TY - JOUR
A1 - Buder, Kristina
A1 - Lapa, Constantin
A1 - Kreissl, Michael C.
A1 - Schirbel, Andreas
A1 - Herrmann, Ken
A1 - Schnack, Alexander
A1 - Bröcker, Eva-Bettina
A1 - Goebeler, Matthias
A1 - Buck, Andreas K.
A1 - Becker, Jürgen C.
T1 - "Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging"
N2 - Background
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment.
Methods
To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT).
Results
SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%).
Conclusion
SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.
KW - Merkel cell carcinoma
KW - Molecular imaging
KW - Somatostatin receptor expression
KW - Positron emission tomography
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110326
ER -
TY - JOUR
A1 - Zhou, Xiang
A1 - Dierks, Alexander
A1 - Kertels, Olivia
A1 - Kircher, Malte
A1 - Schirbel, Andreas
A1 - Samnick, Samuel
A1 - Buck, Andreas K.
A1 - Knorz, Sebastian
A1 - Böckle, David
A1 - Scheller, Lukas
A1 - Messerschmidt, Janin
A1 - Barakat, Mohammad
A1 - Kortüm, K. Martin
A1 - Rasche, Leo
A1 - Einsele, Hermann
A1 - Lapa, Constantin
T1 - 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features
JF - Cancers
N2 - This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.
KW - 18F-FDG PET/CT
KW - 11C-Methionine PET/CT
KW - 68Ga-Pentixafor PET/CT
KW - smoldering myeloma
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211240
SN - 2072-6694
VL - 12
IS - 8
ER -
TY - JOUR
A1 - Wondergem, Marielle J.
A1 - Herrmann, Ken
A1 - Syrbu, Sergei
A1 - Zijlstra, Josée M.
A1 - Hoetjes, Nikie
A1 - Hoekstra, Otto S.
A1 - Cillessen, Saskia A. G. M.
A1 - Moesbergen, Laura M.
A1 - Buck, Andreas K.
A1 - Vose, Julie M.
A1 - Juweid, Malik E.
T1 - 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
JF - EJNMMI Research
N2 - BACKGROUND:
We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).
METHODS:
We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.
RESULTS:
18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.
CONCLUSIONS:
This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
KW - 18-F-fluorothymidine uptake
KW - positron emission tomography
KW - follicular lymphoma
KW - non-Hodgkin's lymphoma
KW - DNA repair
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121233
VL - 4
ER -
TY - JOUR
A1 - Nose, Naoko
A1 - Nogami, Suguru
A1 - Koshino, Kazuhiro
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Kashima, Soki
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Fukuchi, Kazuki
A1 - Higuchi, Takahiro
T1 - [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
JF - Scientific Reports
N2 - Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
KW - biomarkers
KW - molecular medicine
KW - stem-cell research
KW - stem cells
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260590
VL - 11
IS - 1
ER -
TY - JOUR
A1 - Breun, Maria
A1 - Monoranu, Camelia M.
A1 - Kessler, Almuth F.
A1 - Matthies, Cordula
A1 - Löhr, Mario
A1 - Hagemann, Carsten
A1 - Schirbel, Andreas
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Buck, Andreas K.
A1 - Wester, Hans-Jürgen
A1 - Ernestus, Ralf-Ingo
A1 - Lapa, Constantin
T1 - [\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas
JF - Frontiers in Oncology
N2 - We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.
Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.
Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.
Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
KW - vestibular schwannoma
KW - CXCR4
KW - PET/CT
KW - molecular imaging
KW - Pentixafor
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201863
VL - 9
IS - 503
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Schreder, Martin
A1 - Schirbel, Andreas
A1 - Samnick, Samuel
A1 - Kortüm, Klaus Martin
A1 - Herrmann, Ken
A1 - Kropf, Saskia
A1 - Einsele, Herrmann
A1 - Buck, Andreas K.
A1 - Wester, Hans-Jürgen
A1 - Knop, Stefan
A1 - Lückerath, Katharina
T1 - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
JF - Theranostics
N2 - Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.
Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.
[\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018).
[\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
KW - medicine
KW - multiple myeloma
KW - FDG
KW - molecular imaging
KW - CXCR4
KW - PET
KW - radionuclide therapy
KW - theranostics
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106
VL - 7
IS - 1
ER -
TY - THES
A1 - Brumberg [geb. Ichouh], Dalma
T1 - \(^{11}\)C-MET und \(^{18}\)F-FDG: \(In\) \(vitro\) Vergleich zur Bildgebung beim Multiplen Myelom im Kontext biologischer Charakteristika
T1 - Imaging multiple myeloma with \(^{11}\)C-MET and \(^{18}\)F-FDG: \(In\) \(vitro\) comparison in the context of biological characteristics
N2 - Das Multiple Myelom ist eine hämatologische Erkrankung, die durch die Proliferation von Plasmazellen und die Produktion von Antikörpern oder deren Leichtketten gekennzeichnet ist. Eine frühe Diagnosestellung durch Detektion sowohl intra- als auch extramedullärer Manifestationen ist für die Einleitung einer effektiven Therapie von entscheidender Bedeutung. Ebenso bedeutsam ist ein wirksames Therapiemonitoring. Wichtige diagnostische Modalitäten sind bei beiden Fragestellungen tomografische, bildgebende Verfahren. Hierbei wurde die Effektivität der 18F-FDG-PET/CT im Rahmen der Diagnose, des Stagings und der Prognoseabschätzung bereits nachgewiesen. Dennoch ist ihr klinischer Nutzen durch die geringe Sensitivität bei Detektion von diffusem Knochenmarksbefall und Vorliegen sowohl falsch positiver als auch falsch negativer Befunde limitiert.
Die vorliegende Arbeit hat untersucht, ob der aminosäurebasierte Tracer 11C-MET über spezifische Eigenschaften verfügt, die eine höhere Sensitivität und Spezifität in der Detektion von Myelomzellen ermöglichen und ob der Radioligand dem etablierten Glukoseanalogon 18F-FDG überlegen ist. Hierfür wurden drei etablierte humane Myelomzelllinien, sowohl nativ als auch nach 48-stündiger Therapie mit dem Proteasominhibitor Carfilzomib, mit 18F-FDG und 11C-MET inkubiert und mithilfe eines Gammastrahlungszählers beurteilt. Zudem wurde untersucht, ob die Traceraufnahme mit spezifischen Charakteristika der Tumorbiologie korreliert. So wurde die Oberflächenexpression von CD138 und CXCR4, die intrazelluläre Expression der Leichtketten κ/λ und die Proliferation der Zelllinien mittels Durchflusszytometrie vor und nach Behandlung mit Carfilzomib eruiert.
Die unbehandelten Zellen zeigten, verglichen zu 18F-FDG, bereits nach kürzester Inkubationsdauer eine 3-3,5-fach höhere 11C-MET Retention. Weiterhin zeigte sich die 11C-MET-Aufnahme nach Behandlung aller Zellreihen insgesamt marginal höher als die 18F-FDG-Aufnahme, während die Reduktion der 11C-MET-Anreicherung im prä- zu posttherapeutischen Vergleich für alle drei Zelllinien signifikant war.
Eine mögliche Erklärung für diese Beobachtungen liefert die Myelombiologie: eine erhöhte Aufnahme der radioaktiv markierten Aminosäure durch MM-Zellen könnte durch eine Zunahme der Zellproliferation und insbesondere durch eine Steigerung der Proteinsynthese im Rahmen der überschießenden Produktion von M-Protein bedingt sein. In Zusammenschau könnte 11C-MET mit höherer Sensitivität Myelommanifestationen detektieren, wodurch ggf. Läsionen mit geringem Metabolismus dargestellt und eine bessere Beurteilung des Krankheitspogresses erfolgen könnte. Zudem bietet für den klinischen Einsatz die – verglichen zu 18F-FDG – größere Differenz der 11C-MET-Retention zwischen prä- und posttherapeutischer Messung die Möglichkeit einer besseren Beurteilbarkeit des Therapieansprechens. 11C-MET birgt ggf. das Potential auch minimale aktive Restherde zu detektieren und damit Patienten einem individualisierten Therapiekonzept zuzuführen.
Ein Zusammenhang zwischen den untersuchten Biomarkern und der 11C-MET Retention bzw. deren Abnahme nach Behandlung konnte nicht gezeigt werden. Somit sollten für 11C-MET andere Biomarker herangezogen werden, um diese mit der Bildgebung zu korrelieren und zu bewerten.
N2 - Multiple myeloma is a heterogeneous lymphoproliferative disease, which is characterized by an uncontrolled proliferation of clonal plasma cells. It is both essential to diagnose the disease at an early stage in order to prevent organ damage and to monitor therapy to adjust and individualize it. Imaging modalities like 18F-FDG-PET/CT play an important role for these purposes. However, its clinical benefit is limited due to the low detection rate of diffuse bone marrow invasion and false positive or negative findings. To overcome these limitations, we analysed if the amino acid-based tracer 11C-MET has specific features to reach a higher sensitivity and specificity in detecting myeloma cells. Therefore, three established human myeloma cell lines were incubated with 18F-FDG and 11C-MET natively without and after therapy with the proteasome inhibitor Carfilzomib and evaluated via gamma counter. The results showed a higher 11C-MET-uptake in untreated cells after a short time, a higher uptake after treatment with Carfilzomib and a significant reduction pre- to post therapy compared to 18F-FDG. These results assume that 11C-MET has the potential to be more sensitive in detecting myeloma manifestations as well as for the monitoring of disease activity during and after treatment. Furthermore, it might also have the potential to visualize minimal residual disease after treatment. This could lead to an early adaption of therapy and thereby may extend progression free survival.
This study also investigated the relationship between specific biological characteristics of multiple myeloma (surface expression of CD138 and CXCR4, intracellular light chain production and proliferation rate) and radioligand uptake. A correlation between the markers and the uptake could not be proven, so that we assume that other biomarkers should be considered and correlated with 11C-MET to reflect tumor biology and verify possible prognostic markers.
KW - Multiples Myelom
KW - 11C-Methionin
KW - Positronenemissionstomographie
KW - 18F-FDG
KW - CD138
KW - CXCR4
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181843
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Garcia-Velloso, Maria J.
A1 - Lückerath, Katharina
A1 - Samnick, Samuel
A1 - Schreder, Martin
A1 - Otero, Paula Rodriguez
A1 - Schmid, Jan-Stefan
A1 - Herrmann, Ken
A1 - Knop, Stefan
A1 - Buck, Andreas K.
A1 - Einsele, Hermann
A1 - San-Miguel, Jesus
A1 - Kortüm, Klaus Martin
T1 - \(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions
JF - Theranostics
N2 - \(^{11}\)C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to \(^{18}\)F-2`-deoxy-2`-fluoro-D-glucose (FDG).
78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available.
MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases.
MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72).
This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.
KW - medicine
KW - PET/CT
KW - \(^{11}\)C-methionine
KW - multiple myeloma
KW - FDG
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172038
VL - 7
IS - 11
ER -
TY - JOUR
A1 - Lückerath, Katharina
A1 - Lapa, Constantin
A1 - Albert, Christa
A1 - Herrmann, Ken
A1 - Jörg, Gerhard
A1 - Samnick, Samuel
A1 - Einsele, Herrmann
A1 - Knop, Stefan
A1 - Buck, Andreas K.
T1 - \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
JF - Oncotarget
N2 - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
KW - positron emission tomography
KW - imaging techniques
KW - experience
KW - \(^{11}\)C-Methionine-PET
KW - treatment response
KW - molecular imaging
KW - multiple myeloma
KW - management
KW - \(^{18}\)F-FDG PET/CT
KW - bone disease
KW - stem-cell transplantation
KW - esophagogastric junction
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148688
VL - 6
IS - 10
ER -
TY - JOUR
A1 - Beykan, Seval
A1 - Dam, Jan S.
A1 - Eberlein, Uta
A1 - Kaufmann, Jens
A1 - Kjærgaard, Benedict
A1 - Jødal, Lars
A1 - Bouterfa, Hakim
A1 - Bejot, Romain
A1 - Lassmann, Michael
A1 - Jensen, Svend Borup
T1 - \(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model
JF - EJNMMI Research
N2 - Background
\(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications.
Results
\(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels.
Conclusions
The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.
KW - lutetium-177
KW - JR11
KW - antagonist
KW - dosimetry
KW - neuroendocrine tumor (NET)
KW - OPS201
KW - pig model
KW - PRRT
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146888
VL - 6
IS - 50
ER -
TY - JOUR
A1 - Morales-Lozano, Maria I.
A1 - Viering, Oliver
A1 - Samnick, Samuel
A1 - Rodriguez-Otero, Paula
A1 - Buck, Andreas K.
A1 - Marcos-Jubilar, Maria
A1 - Rasche, Leo
A1 - Prieto, Elena
A1 - Kortüm, K. Martin
A1 - San-Miguel, Jesus
A1 - Garcia-Velloso, Maria J.
A1 - Lapa, Constantin
T1 - \(^{18}\)F-FDG and \(^{11}\)C-methionine PET/CT in newly diagnosed multiple myeloma patients: comparison of volume-based PET biomarkers
JF - Cancers
N2 - \(^{11}\)C-methionine (\(^{11}\)C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of \(^{11}\)C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to \(^{18}\)F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone \(^{11}\)C-MET and \(^{18}\)F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion \(^{11}\)C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), \(^{11}\)C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in \(^{11}\)C-MET than in \(^{18}\)F-FDG (p < 0.05, respectively). \(^{11}\)C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that \(^{11}\)C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than \(^{18}\)F-FDG. Its implications for prognosis evaluation need further investigation.
KW - multiple myeloma
KW - methionine
KW - total lesion glycolysis (TLG)
KW - metabolic tumor volume (MTV)
KW - total lesion methionine uptake (TLMU)
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203686
SN - 2072-6694
VL - 12
IS - 4
ER -
TY - THES
A1 - Viering, Oliver
T1 - \(^{18}\)F-Fluordesoxyglucose- und \(^{11}\)C-Methionin-PET/CT bei Patient/-innen mit neu diagnostiziertem Multiplen Myelom: Ein Vergleich volumenbasierter PET-Biomarker
T1 - \(^{18}\)F-fluorodeoxyglucose and \(^{11}\)C-methionine PET/CT in patients with newly diagnosed multiple myeloma: A comparison of volume-based PET biomarkers
N2 - 11C-Methionin (11C-MET) ist ein alternatives Radiopharmakon für die Positronen-Emissions-Tomographie (PET) zur Beurteilung der Krankheitsaktivität bei Patient/-innen mit Multiplem Myelom (MM). Frühe Daten legen eine höhere Sensitivität und Spezifität als bei dem bisherigen Standardtracer 18F-Fluordesoxyglucose (18F-FDG) nahe. Es fehlen bislang jedoch Untersuchungen, welche die neuen, aus PET-Daten abgeleiteten Parameter „metabolic tumor volume“ (MTV) und „total lesion glycolysis / total lesion methionin uptake“ (TLG/TLMU) in diesen Vergleich miteinbeziehen. In früheren Studien konnte bereits eine prognostische Aussagekraft dieser neuen Imaging Parameter für die 18F-FDG-PET/CT gezeigt werden. Das Ziel dieser bizentrischen Studie war es, die sich im Rahmen bisheriger Studienergebnisse andeutende Überlegenheit von 11C-MET für das Staging des MM zu überprüfen und seine Eignung für die Bewertung von metabolischen Imaging Parametern im Vergleich zu 18F-FDG zu untersuchen.
Zweiundzwanzig Patient/-innen mit neu diagnostiziertem unbehandelten MM, davon 15 Patient/-innen des Universitätsklinikums Würzburg und sieben Patient/-innen der Clinica Universidad de Navarra in Pamplona, die eine doppelte PET/CT-Bildgebung unter Verwendung der beiden Tracer 11C-MET und 18F-FDG innerhalb eines Zeitraums von maximal 14 Tagen erhalten hatten, wurden retrospektiv durch den Doktoranden (Oliver Viering) sowie eine nuklearmedizinische Assistenzärztin (Maria I. Morales-Lozano) und im Anschluss durch je eine PET/CT-Expert/-in des Universitätsklinikums Würzburg (Constantin Lapa) und der Clinica Universidad de Navarra (Maria J. Garcia-Velloso) untersucht.
Hierfür wurden die 18F-FDG- und 11C-MET-PET/CT-Aufnahmen einer dreidimensionalen Analyse mit Hilfe des "PET/CT-Viewer Beth Israel for FIJI" unterzogen. Diese open source Software ermöglichte die Berechnung von SUVmean, SUVmax und SUVpeak sowie der neuen Imaging Biomarker MTV und TLG/TLMU. Die genannten PET-Parameter wurden mit klinischen und laborchemischen Parametern (Hämoglobin, Calcium, Kreatinin, CRP, β2-Mikroglobulin, Albumin, M-Gradient/M-Protein, Knochenmarkinfiltration, LDH, freier Leichtketten-quotient, R-ISS, zytogenetisches Risiko) korreliert, welche in früheren Studien als prognostisch relevante Parameter der Myelom-Erkrankung identifiziert worden waren.
Bei elf der 22 Patient/-innen (50 %) wurden mithilfe von 11C-MET mehr fokale Läsionen als mit 18F-FDG nachgewiesen (p < 0,01), daneben konnte bei einer größeren Zahl von Patient/-innen eine diffuse Knochenmarkinfiltration durch die malignen Plasmazellen identifiziert werden (11C-MET: 19, 18F-FDG: 12). Sowohl die SUV-Parameter (SUVmean, SUVmax und SUVpeak) als auch die neuen Imaging Parameter (TMTV und TLG/TLMU) waren bei der 11C-MET- signifikant höher als bei der 18F-FDG-PET/CT (p < 0,05).
In Bezug auf die neuen Imaging Parameter zeigten sich für 11C-MET häufiger signifikante Korrelationen mit den prognostisch relevanten klinischen und laborchemischen Parametern als für 18F-FDG. Bei TMTV konnten für die 11C-MET-PET/CT signifikante Korrelationen für β2-Mikroglobulin (p = 0,006), die M-Komponente (p = 0,003), den Grad der Knochenmarkinfiltration (p = 0,007) und das Serum-Hämoglobin (p = 0,016) gefunden werden, wohingegen sich bei 18F-FDG lediglich eine signifikante Korrelation für β2-Mikroglobulin (p = 0,044) zeigte. In Bezug auf die TLG/TLMU konnten bei 18F-FDG keine signifikanten Korrelationen zwischen TLG und den klinischen und laborchemischen Parametern nachgewiesen werden. Bei 11C-MET zeigten sich hingegen signifikante Korrelationen zwischen dem TLMU und der Kalzium-Konzentration im Serum (p = 0,028), dem β2-Mikroglobulin (p = 0,047), der M-Komponente (p = 0,033) und dem Grad der Knochenmarkinfiltration (p = 0,041).
Trotz zahlreicher Limitationen dieser Arbeit, wie etwa der geringen Patientenzahl und des retrospektiven Charakters der Auswertung bekräftigt auch diese Studie in Übereinstimmung mit den bisherigen Studienergebnissen, dass 11C-MET im Vergleich zu 18F-FDG ein sensitiverer Marker für die Beurteilung der Myelom-Tumorlast sein könnte. Eine Untersuchung der prognostischen Aussagekraft von 11C-MET in Bezug auf progressionsfreies- und Gesamtüberleben im Zuge der primären Bildgebung der Erkrankung war aufgrund der kurzen Nachbeobachtungszeit und der Heterogenität der Behandlung, welche die Patient/-innen im Anschluss an die Staging-Untersuchungen erhalten hatten, nicht möglich und muss im Rahmen zukünftiger, insbesondere prospektiver Studien weiter untersucht werden.
N2 - 11C-methionine (11C-MET) is an alternative radiopharmaceutical for positron emission tomography / computed tomography (PET/CT) to assess disease activity in patients with multiple myeloma (MM). Early data suggest a higher sensitivity and specificity than with the previous standard tracer 18F-fluorodeoxyglucose (18F-FDG). However, studies that include the new parameters "metabolic tumour volume" (MTV) and "total lesion glycolysis / total lesion methionine uptake" (TLG/TLMU) are still lacking in this comparison. Previous studies have already shown a prognostic significance of these new imaging parameters for 18F-FDG-PET/CT. The aim of this bicentre study was to test the apparent superiority of 11C-MET for the staging of MM in the context of previous study results and to investigate its suitability for the assessment of metabolic imaging parameters in comparison to 18F-FDG.
Twenty-two patients with newly diagnosed untreated MM, including 15 patients from the University Hospital of Würzburg and seven patients from the Clinica Universidad de Navarra in Pamplona, who had received double PET/CT imaging using the two tracers 11C-MET and 18F-FDG within a maximum period of 14 days, were retrospectively evaluated.
For this purpose, the 18F-FDG and 11C-MET PET/CT images were analysed by using the "PET/CT Viewer Beth Israel for FIJI". This open source software enabled the calculation of SUVmean, SUVmax and SUVpeak as well as the new imaging biomarkers MTV and TLG/TLMU. These PET parameters were correlated with clinical and laboratory parameters (haemoglobin, calcium, creatinine, CRP, β2-microglobulin, albumin, M-gradient/M-protein, bone marrow infiltration, LDH, free light chain ratio, R-ISS, cytogenetic risk), which had been identified as prognostically relevant parameters of myeloma disease in previous studies.
In eleven of the 22 patients 11C-MET detected more focal lesions than 18F-FDG (p < 0.01) and a larger number of diffuse bone marrow infiltration by malignant plasma cells was identified (11C-MET: 19, 18F-FDG: 12). Both the SUV parameters (SUVmean, SUVmax and SUVpeak) and the new imaging parameters (TMTV and TLG/TLMU) were significantly higher in 11C-MET than in 18F-FDG PET/CT (p < 0.05).
With regard to the new imaging parameters, significant correlations with the prognostically relevant clinical and laboratory parameters were shown more frequently for 11C-MET than for 18F-FDG. In TMTV, significant correlations were found for 11C-MET PET/CT for β2-microglobulin (p = 0.006), the M-component (p = 0.003), the level of bone marrow infiltration (p = 0.007) and serum haemoglobin (p = 0.016), whereas 18F-FDG only showed a significant correlation for β2-microglobulin (p = 0.044). With regard to TLG/TLMU, no significant correlations between TLG and the clinical and laboratory parameters could be demonstrated for 18F-FDG. In contrast, 11C-MET showed significant correlations between TLMU and serum calcium concentration (p = 0.028), β2-microglobulin (p = 0.047), M-component (p = 0.033) and the level of bone marrow infiltration (p = 0.041).
Despite numerous limitations of this work, such as the small number of patients and the retrospective analysis, this study also confirms that 11C-MET could be a more sensitive marker for the assessment of MM compared to 18F-FDG. An investigation of the prognostic significance of 11C-MET with regard to progression-free and overall survival in the course of primary imaging was not possible due to the short follow-up period and the heterogeneity of the treatment the patients received following PET/CT imaging and therefore must be investigated in the context of future studies.
KW - Plasmozytom
KW - Positronen-Emissions-Tomografie
KW - PET/CT
KW - Multiples Myelom
KW - \(^{18}\)F-Fluordesoxyglucose
KW - \(^{11}\)C-Methionin
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318032
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Sheikbahaei, Sara
A1 - Higuchi, Takahiro
A1 - Giesel, Frederik L.
A1 - Behr, Spencer
A1 - Drzezga, Alexander
A1 - Kimura, Hiroyuki
A1 - Buck, Andreas K.
A1 - Bengel, Frank M.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
T1 - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
JF - Theranostics
N2 - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
KW - Radiofluorine
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - \(^{18}\)F
KW - PSMA
KW - \(^{68}\)Ga
KW - theranostics
KW - radioligand therapy
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559
SN - 1838-7640
VL - 10
IS - 1
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Lückerath, Katharina
A1 - Kleinlein, Irene
A1 - Monoranu, Camelia Maria
A1 - Linsenmann, Thomas
A1 - Kessler, Almuth F.
A1 - Rudelius, Martina
A1 - Kropf, Saskia
A1 - Buck, Andreas K.
A1 - Ernestus, Ralf-Ingo
A1 - Wester, Hans-Jürgen
A1 - Löhr, Mario
A1 - Herrmann, Ken
T1 - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
JF - Theranostics
N2 - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
KW - imaging
KW - chemokine receptor-4
KW - glioblastoma
KW - positron emission tomography/computed tomography
KW - \(^{68}\)Ga-Pentixafor
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174
VL - 6
IS - 3
ER -
TY - JOUR
A1 - Baur, Johannes
A1 - Schedelbeck, Ulla
A1 - Pulzer, Alina
A1 - Bluemel, Christina
A1 - Wild, Vanessa
A1 - Fassnacht, Martin
A1 - Steger, U.
T1 - A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma
JF - BMC Surgery
N2 - Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
KW - surgical treatment
KW - adrenocortical
KW - carcinoma metastases to pancreas
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126130
VL - 15
IS - 93
ER -
TY - JOUR
A1 - Tran-Gia, Johannes
A1 - Denis-Bacelar, Ana M.
A1 - Ferreira, Kelley M.
A1 - Robinson, Andrew P.
A1 - Calvert, Nicholas
A1 - Fenwick, Andrew J.
A1 - Finocchiaro, Domenico
A1 - Fioroni, Federica
A1 - Grassi, Elisa
A1 - Heetun, Warda
A1 - Jewitt, Stephanie J.
A1 - Kotzassarlidou, Maria
A1 - Ljungberg, Michael
A1 - McGowan, Daniel R.
A1 - Scott, Nathaniel
A1 - Scuffham, James
A1 - Gleisner, Katarina Sjögreen
A1 - Tipping, Jill
A1 - Wevrett, Jill
A1 - Lassmann, Michael
T1 - A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project
JF - EJNMMI Physics
N2 - Purpose
Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time–activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative \(^{177}\)Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise.
Methods
The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities.
Results
Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla.
Conclusion
This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.
KW - quantitative SPECT/CT
KW - 177Lu SPECT/CT imaging
KW - standardization of SPECT/CT imaging
KW - harmonization of SPECT/CT imaging
KW - international multicenter comparison exercise
KW - traceability of SPECT/CT imaging
KW - molecular radiotherapy (MRT)
KW - 3D printing
KW - phantom
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270380
VL - 8
ER -
TY - JOUR
A1 - Wenz, Jan
A1 - Arndt, Felix
A1 - Samnick, Samuel
T1 - A new concept for the production of \(^{11}\)C-labelled radiotracers
JF - EJNMMI Radiopharmacy and Chemistry
N2 - Background
The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate.
Results
The target gas purification of cyclotron produced [\(^{11}\)C]CO\(_2\) and subsequent conversion to [\(^{11}\)C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[\(^{11}\)C]choline and L-S-methyl-[\(^{11}\)C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [\(^{11}\)C]MeI. After 18 min N-methyl-[\(^{11}\)C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[\(^{11}\)C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [\(^{11}\)C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [\(^{11}\)C]CO\(_2\) was passed through. After complete release of [\(^{11}\)C]CO\(_2\) the reaction mixture was quenched with water and guided through a series of ion exchangers (H\(^+\), Ag\(^+\) and OH\(^−\)). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [\(^{11}\)C]CO\(_2\) before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [\(^{11}\)C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%.
Conclusion
Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate.
KW - carboxylation
KW - methylation
KW - Carbon-11
KW - isotopes
KW - isotopic labelling
KW - radiopharmaceuticals
KW - radiochemistry
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300731
VL - 7
ER -
TY - JOUR
A1 - Drozd, Valentina
A1 - Saenko, Vladimir
A1 - Branovan, Daniel I.
A1 - Brown, Kate
A1 - Yamashita, Shunichi
A1 - Reiners, Christoph
T1 - A search for causes of rising incidence of differentiated thyroid cancer in children and adolescents after Chernobyl and Fukushima: comparison of the clinical features and their relevance for treatment and prognosis
JF - International Journal of Environmental Research and Public Health
N2 - The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4–5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.
KW - rising incidence of thyroid cancer
KW - screening and overdiagnosis
KW - pediatric thyroid cancer after Chernobyl and Fukushima
KW - nitrate and thyroid carcinogenesis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234247
SN - 1660-4601
VL - 18
IS - 7
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Andree, Christian
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
A1 - Pienta, Kenneth J.
T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
T2 - Urology - The Gold Journal
N2 - No abstract available.
KW - 18F-DCFPyL
KW - Virchow Node
KW - PSMA-PET
KW - Virchow Node
KW - Positron Emission Tomography
KW - Prostate Cancer
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161103
SN - 0090-4295
N1 - This is the accepted manuscript of Rudolf Werner, Christian Andree, Mehrbod S. Javadi, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi, Martin G. Pomper, Michael A.Gorin, Steven P.Rowe, Kenneth J. Pienta: A Voice From the Past: Re-Discovering the Virchow Node with PSMA-Targeted 18F-DCFPyL PET Imaging. Published in Urology 117(2018), p. 18-21. https://doi.org/10.1016/j.urology.2018.03.030
N1 - Die finale Version dieses Artikels steht unter https://doi.org/10.1016/j.urology.2018.03.030 oder https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-164632 open access zur Verfügung.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Andree, Christian
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
A1 - Pienta, Kenneth J.
T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
JF - Urology - The Gold Journal
N2 - No abstract available.
KW - 18F-DCFPyL
KW - PET
KW - PSMA-PET
KW - Positron Emission Tomography
KW - Prostate Cancer
KW - Virchow Node
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164632
SN - 0090-4295
VL - 117
ER -
TY - JOUR
A1 - Leube, Julian
A1 - Gustafsson, Johan
A1 - Lassmann, Michael
A1 - Salas-Ramirez, Maikol
A1 - Tran-Gia, Johannes
T1 - Analysis of a deep learning-based method for generation of SPECT projections based on a large Monte Carlo simulated dataset
JF - EJNMMI Physics
N2 - Background
In recent years, a lot of effort has been put in the enhancement of medical imaging using artificial intelligence. However, limited patient data in combination with the unavailability of a ground truth often pose a challenge to a systematic validation of such methodologies. The goal of this work was to investigate a recently proposed method for an artificial intelligence-based generation of synthetic SPECT projections, for acceleration of the image acquisition process based on a large dataset of realistic SPECT simulations.
Methods
A database of 10,000 SPECT projection datasets of heterogeneous activity distributions of randomly placed random shapes was simulated for a clinical SPECT/CT system using the SIMIND Monte Carlo program. Synthetic projections at fixed angular increments from a set of input projections at evenly distributed angles were generated by different u-shaped convolutional neural networks (u-nets). These u-nets differed in noise realization used for the training data, number of input projections, projection angle increment, and number of training/validation datasets. Synthetic projections were generated for 500 test projection datasets for each u-net, and a quantitative analysis was performed using statistical hypothesis tests based on structural similarity index measure and normalized root-mean-squared error. Additional simulations with varying detector orbits were performed on a subset of the dataset to study the effect of the detector orbit on the performance of the methodology. For verification of the results, the u-nets were applied to Jaszczak and NEMA physical phantom data obtained on a clinical SPECT/CT system.
Results
No statistically significant differences were observed between u-nets trained with different noise realizations. In contrast, a statistically significant deterioration was found for training with a small subset (400 datasets) of the 10,000 simulated projection datasets in comparison with using a large subset (9500 datasets) for training. A good agreement between synthetic (i.e., u-net generated) and simulated projections before adding noise demonstrates a denoising effect. Finally, the physical phantom measurements show that our findings also apply for projections measured on a clinical SPECT/CT system.
Conclusion
Our study shows the large potential of u-nets for accelerating SPECT/CT imaging. In addition, our analysis numerically reveals a denoising effect when generating synthetic projections with a u-net. Clinically interesting, the methodology has proven robust against camera orbit deviations in a clinically realistic range. Lastly, we found that a small number of training samples (e.g., ~ 400 datasets) may not be sufficient for reliable generalization of the u-net.
KW - 177Lu
KW - Monte Carlo
KW - SPECT
KW - Deep learning
KW - Denoising
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300697
SN - 2197-7364
VL - 9
ER -
TY - JOUR
A1 - Schadt, Fabian
A1 - Israel, Ina
A1 - Beez, Alexandra
A1 - Alushi, Kastriot
A1 - Weiland, Judith
A1 - Ernestus, Ralf-Ingo
A1 - Westermaier, Thomas
A1 - Samnick, Samuel
A1 - Lilla, Nadine
T1 - Analysis of cerebral glucose metabolism following experimental subarachnoid hemorrhage over 7 days
JF - Scientific Reports
N2 - Little is known about changes in brain metabolism following SAH, possibly leading towards secondary brain damage. Despite sustained progress in the last decade, analysis of in vivo acquired data still remains challenging. The present interdisciplinary study uses a semi-automated data analysis tool analyzing imaging data independently from the administrated radiotracer. The uptake of 2-[18F]Fluoro-2-deoxy-glucose ([\(^{18}\)F]FDG) was evaluated in different brain regions in 14 male Sprague–Dawley rats, randomized into two groups: (1) SAH induced by the endovascular filament model and (2) sham operated controls. Serial [\(^{18}\)F]FDG-PET measurements were carried out. Quantitative image analysis was performed by uptake ratio using a self-developed MRI-template based data analysis tool. SAH animals showed significantly higher [\(^{18}\)F]FDG accumulation in gray matter, neocortex and olfactory system as compared to animals of the sham group, while white matter and basal forebrain region showed significant reduced tracer accumulation in SAH animals. All significant metabolic changes were visualized from 3 h, over 24 h (day 1), day 4 and day 7 following SAH/sham operation. This [\(^{18}\)F]FDG-PET study provides important insights into glucose metabolism alterations following SAH—for the first time in different brain regions and up to day 7 during course of disease.
KW - SAH
KW - metabolism
KW - brain
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300725
VL - 13
IS - 1
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Weinzierl, Franz-Xaver
A1 - Seitz, Anna Katharina
A1 - Kübler, Hubert
A1 - Essler, Markus
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
T1 - Any decline in prostate-specific antigen levels identifies survivors scheduled for prostate-specific membrane antigen-directed radioligand therapy
JF - The Prostate
N2 - Background
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS).
Materials and Methods
In this bicentric analysis, we included 184 mCRPC patients treated with \(^{177}\)Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan–Meier curves and log-rank comparison.
Results
A total of 114/184 patients (62.0%) showed any PSA decline (PSA response >50%, 55/184 [29.9%]). For individuals exhibiting a PSA decline >50%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95% confidence interval [95% CI] = 0.44–0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95% CI = 0.25–0.60; p < 0.001).
Conclusions
In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50%, RLT should be continued.
KW - prostate cancer
KW - theranostics
KW - PSMA‐617
KW - PSA response
KW - PSMA I&T
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318766
VL - 82
IS - 14
SP - 1406
EP - 1412
ER -
TY - JOUR
A1 - Eilsberger, Friederike
A1 - Kreissl, Michael C.
A1 - Reiners, Christoph
A1 - Holzgreve, Adrien
A1 - Luster, Markus
A1 - Pfestroff, Andreas
T1 - Application of the American Thyroid Association risk assessment in patients with differentiated thyroid carcinoma in a German population
JF - Biomedicines
N2 - Background: The American Thyroid Association (ATA) uses criteria to assess the risk for persistent disease in differentiated thyroid carcinoma (DTC) after radioiodine therapy (RAI). There are no data available showing that this classification can be adopted unadjusted by Germany. Aim: The aim of our study is to investigate whether the ATA classification can be applied to a German population for short-term prognosis. Furthermore, we investigated the influence of an age cutoff value. Methods: We retrospectively analyzed 121 patients who were referred to our tertiary referral center. Patients were classified into risk categories, and the therapy response was determined according to ATA. Results: A total of 73/83 (88%) ATA low-risk patients and 12/19 (63%) intermediate-risk patients showed an excellent response; 2/19 (11%) high-risk patients had a biochemical, and 6 (31%) had a structural incomplete response. Of all 39 patients ≥55 years, 84% had an excellent response. Using a cut off of 50 years, 50/62 (81%) of the older patients showed an excellent response. Conclusion: The ATA risk classification is able to estimate the response to RAI therapy in a German population. A shift from 55 to 50 years as an age cutoff value does not result in any relevant change in the treatment response.
KW - differentiated thyroid cancer
KW - American Thyroid Association
KW - German population
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311226
SN - 2227-9059
VL - 11
IS - 3
ER -
TY - THES
A1 - Eißler, Christoph Marcel
T1 - Assessment of the left ventricular systolic and diastolic function in rats using electrocardiogram-gated cardiac positron emission tomography
T1 - Bestimmung der linksventrikulären systolischen und diastolischen Funktion in Ratten durch Elektrokardiogramm-getriggerte kardiale Positronen-Emissions-Tomographie
N2 - DD is a cardiac disturbance, which has gained increasing importance in recent years due to its important role in different cardiac disease and cardiomyopathies including ischemic cardiomyopathy, arterial hypertension and diabetic cardiomyopathy.
ECG-gated 18F-FDG PET is an imaging technique, that can distinguish between districts of myocardial viability and myocardial scars and further provides information of great interest on the efficacy of experimental approaches designed to improve the cardiac function and/or myocardial metabolism in experimental small animal models. However, ECG-gated 18F-FDG PET is a technique whose feasibility in the assessment of the LV diastolic function in small animals has not been a subject of study.
In this thesis, the ability of the ECG-gated 18F-FDG PET for the assessment of both the systolic and diastolic function in eight control rats and in seven ZDF rats, which are an experimental animal model mimicking T2DM conditions and diabetic related complications in humans including DCM, has been investigated The ECG-gated 18F-FDG PET imaging was performed under hyperinsulinemic-euglycemic clamping and the data were stored in list mode files and retrospectively reconstructed. The systolic and diastolic parameters were achieved from the time/volume and the time/filling curve calculated from the software HFV. Additionally, the influence of the number of gates per cardiac cycle on the LV volumes and function parameters has been studied.
Hyperinsulinemic-euglycemic clamp procedure and blood glucose measurement did confirm the development of a manifest diabetes in the ZDF rats at the timepoint of the experiments.
Regarding the systolic parameters, no significant difference could be detected between the ZDF and ZL rats. The values for the CO were similar in both groups, which demonstrates a similar LV systolic function in the ZDF and the ZL rats at the age of 13 weeks. Values for the systolic parameters are in good line with previous PET, MRI and cardiac catheterization-based studies in diabetic rats.
The main finding of this study was that by using in vivo ECG-gated 18F-FDG PET and the software HFV, reliable diastolic parameters could be calculated. Moreover, it was possible to detect the presence of a mild impaired diastolic filling in the ZDF rats in absence of any systolic alteration. This impaired diastolic function in an early stage of diabetes could also be detected by other investigators, who used echocardiography or cardiac catheterization. Therefore, this is the first study showing, that the assessment of the diastolic function in rats can be carried out by ECG-gated 18F-FDG PET imaging.
In conclusion, additionally to calculating LV volumes and LV EF, ECG-gated 18F-FDG PET can evaluate the diastolic function of healthy and diabetic rats and is able to detect a DD in ZDF rats.
N2 - Die DD ist eine Störung der Herzdynamik, welche, aufgrund ihrer Beteiligung in verschiedenen Herzerkrankungen und Kardiomyopathien wie der ischämischen Kardiomyopathie, der arteriellen Hypertonie und der diabetischen Kardiomyopathie, in den letzten Jahren zunehmend in das Interessenzentrum der Herzforschung gerückt ist.
Die EKG-getriggerte 18F-FDG PET ist eine Bildgebungsmethode, welche die Unterscheidung von vitalem Myokard und Narben ermöglicht und zusätzlich noch in der Lage ist, wichtige Informationen zu erheben, welche von Bedeutung für die Beurteilung von experimentelle Behandlungen zur Verbesserung der Herzfunktion und/oder des kardialen Stoffwechsels in präklinischen Tiermodellen sind. Trotz dieser Möglichkeiten wurde bisher noch nicht die Fähigkeit der EKG-getriggerten 18F-FDG PET zur Bestimmung der LV diastoischen Funktion in Kleintiermodellen untersucht.
Deshalb wurde in dieser Arbeit das Potential der EKG-getriggerten 18F-FDG PET in Bezug auf die Bestimmung der LV systolischen und diastolischen Funktion in acht Kontrollratten (ZL) und sieben ZDF-Ratten, welche eine experimentelles Tiermodell für T2DM und die damit verbundenen Komplikationen einschließlich der diabetischen Kardiomyopathie sind, untersucht. Die EKG-getriggerte 18F-FDG PET wurde unter der hyperinsulinämischen euglykämischen Klemm Methode durchgeführt, die Daten in „list-mode“ Dateien gespeichert und retrospektiv rekonstruiert. Die Berechnung der LV systolischen und diastolischen Parameter erfolge aus der Zeit-Volumen-Kurve und der Zeit-Füllungs-Kurve durch das Programm HFV. Zudem wurde der Einfluss der pro Rekonstruktion verwendeten „frames“ pro kardialen Zyklus auf die LV Volumina und die linksventrikulären Funktionsparameter untersucht.
Durch die hyperinsulinämische euglykämische Klemm Methode und durch Blutglukose Messungen konnte die Entwicklung eines manifesten Diabetes zum Zeitpunkt der Experimente in den ZDF Ratten nachgewiesen werden.
Es konnte kein signifikanter Unterschied zwischen den systolischen Parametern der ZDF und der ZL Ratten gefunden werden. Der kardiale Auswurf war nahezu identisch in den beiden Gruppen zum Zeitpunkt der Experimente, was eine vergleichbare systolische Funktion in beiden Gruppen demonstriert. Die erhobenen Werte für die systolischen Parameter befinden sich in guter Übereinstimmung mit den Werten der Literatur von vorherigen PET, MRT und Katheter-gestützten Experimenten in diabetischen Rattenmodellen.
Ein wichtiges Ergebnis dieser Arbeit ist die Erhebung von verlässlichen diastolischen Parametern durch den kombinierten Einsatz von EKG-getriggerter 18F-FDG PET und HFV. Zudem war es möglich, eine gestörte diastolische Füllung des LV in den ZDF Ratten nachzuweisen, in Abwesenheit von systolischen Funktionseinschränkungen.
Eine Beeinträchtigung der diastolischen Funktion in der frühen Phase des Diabetes wurde bereits in anderen Rattenstudien mittels Echokardiografie und Katheter basierten Untersuchungen gezeigt. Dennoch ist dies hier die erste Studie, welche demonstriert, dass die Bestimmung der diastolischen Funktion auch mit Hilfe der EKG-getriggerten 18F-FDG PET durchgeführt werden kann.
In Zusammenfassung lässt sich festhalten, das zusätzlich zu der Bestimmung der LV-Volumina und der LVEF durch EKG-getriggerten 18F-FDG PET auch die Bestimmung der diastolischen Funktion in gesunden und diabetischen Ratten möglich ist und dass durch EKG-getriggerten 18F-FDG PET die Identifikation einer DD in ZDF Ratten möglich ist.
KW - Positronen-Emissions-Tomografie
KW - preclinical PET
KW - ECG-gated PET
KW - diastolic dysfunction
KW - diabetic cardiomyopathy
KW - HFpEF
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219765
ER -
TY - JOUR
A1 - Garg, Tushar
A1 - Werner, Rudolf A.
A1 - Chung, Hyun Woo
A1 - Khatri, Wajahat
A1 - Pienta, Kenneth J.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Saad, Elie
A1 - Rowe, Steven P.
T1 - Association of true positivity with serum prostate-specific antigen levels and other clinical factors in indeterminate PSMA-RADS-3A lesions identified on \(^{18}\)F-DCFPyL PET/CT scans
JF - Tomography
N2 - The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on \(^{18}\)F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0–0.2, 0.2–1, 1–2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59–81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2% vs. 81.9%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12% (95% CI = 73.69–86.16%), and the area under the curve was 71.32% (95% CI = 61.9–80.7%, p < 0.0001). A total of 96.4% (108/112) of patients with positive lesions and 86.4% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial \(^{18}\)F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.
KW - prostate cancer
KW - prostate-specific antigen
KW - PSMA-RADS
KW - \(^{18}\)F-DCFPyL PET/CT
KW - Gleason score
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290510
SN - 2379-139X
VL - 8
IS - 6
SP - 2639
EP - 2647
ER -
TY - JOUR
A1 - Kosmala, Aleksander
A1 - Serfling, Sebastian E.
A1 - Dreher, Niklas
A1 - Lindner, Thomas
A1 - Schirbel, Andreas
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
T1 - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography
JF - Cancers
N2 - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
KW - PET
KW - [\(^{68}\)Ga]Ga-FAPI
KW - theranostics
KW - radioligand therapy
KW - fibroblast activation protein
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154
SN - 2072-6694
VL - 14
IS - 11
ER -
TY - THES
A1 - Münch, Annette
T1 - Auf der Suche nach den verborgenen Jodquellen : Bestimmung des Jodgehaltes in Getränken
T1 - Searching for the hidden Iodine in beverages
N2 - Jod ist ein essentielles Spurenelement, welches der Mensch zur Aufrechterhaltung des ungestörten Schilddrüsenmetabolismus und davon beeinflussten verschiedenen Körperfunktionen benötigt. Weltweit gab und gibt es einen Jodmangel, der schwerwiegende gesundheitliche Folgen für das Individuum und wirtschaftliche Folgen für die Gesundheitssysteme des jeweiligen Landes hat. Auch Deutschland galt mit weiteren europäischen Ländern bis vor wenigen Jahren als Jodmangelgebiet. Durch intensive Aufklärungsarbeit und Programme zur Beseitigung des Jodmangels gelang es, diesen in vielen Ländern zu vermindern. Außer einer generellen Verwendung von Jodsalz in der Lebensmittelproduktion und den Privathaushalten, konnten noch weitere wichtige Jodquellen für die Bevölkerung in verschiedenen Studien belegt werden. Diese Studie beschäftigt sich mit der Ermittlung von Jodgehalt in Alltagsgetränken. Die Ergebnisse sind vergleichbar zu bereits veröffentlichen Studien und zeigen einen hohen Jodgehalt von Milch und Milchgetränken, sowie von Bier und Wein. Kein Jod in größeren Mengen hingegen enthält das regionale Leitungswasser, sowie Mineralwässer und diverse Fruchtsäfte. Somit kann der Verzehr von Milch und Milchgetränken und in Maßen auch Bier und Wein für eine jodreiche Ernährung empfohlen werden. Hingegen sollten Patienten in Vorbereitung zum Beispiel auf eine Radiojodtherapie Milch, Biere und Wein eher meiden und jodarme Getränke bevorzugen.
N2 - Iodine is an essential trace element, which is required to maintain the undisturbed thyroid metabolism. It influences various body functions. Worldwide there is a lack of iodine which has serious health consequences for the individual. There are also economic consequences for the health systems of each country. A few years ago Germany was, with other European countries,a iodine deficiency area. With intensive educational work and programs for the elimination of iodine deficiency, it was possible to reduce the iodine deficiency in many countries. A general use of iodized salt in the food production and households, other important sources of iodine could be found in various studies. This study deals with the determination of iodine content in everyday drinks. The results are comparable to previously published studies and show a high iodine content of milk and milk-based drinks, as well as beer and wine. No iodine in larger amounts, however, contains the local tap water, mineral water and various fruit juices. The consumption of milk, milk-based drinks, beer and wine in moderation can be recommended for an iodine-rich diet. In contrast, patients in preparation for a radioiodine therapie shoud avoid milk, beer and wine.
KW - Iod
KW - Iodgehalt
KW - Getränke
KW - Iodine
KW - iodine content
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85141
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Seitz, Anna Katharina
A1 - Weinzierl, Franz-Xaver
A1 - Serfling, Sebastian E.
A1 - Schirbel, Andreas
A1 - Rowe, Steven P.
A1 - Kübler, Hubert
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - Baseline clinical characteristics predict overall survival in patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I&T during long-term follow-up
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Background
Radioligand therapy (RLT) with \(^{177}\)Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [\(^{177}\)Lu]Lu-PSMA I&T RLT in a long-term follow-up.
Materials and methods
Ninety-two mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval\(_{Diagnosis-RLT}\), per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan–Meier analyses.
Results
Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02–1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01–1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06–1.26; P = 0.001), and interval\(_{Diagnosis-RLT}\) (HR, 0.95, 95% CI 0.91–0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval\(_{Diagnosis-RLT}\), 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan–Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval\(_{Diagnosis-RLT}\) (P ≤ 0.01, respectively).
Conclusion
In mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [\(^{177}\)Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.
KW - PSMA
KW - prostate cancer
KW - [177Lu]Lu-PSMA I&T
KW - radioligand therapy
KW - overall survival
KW - prediction
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324573
VL - 49
IS - 12
ER -
TY - THES
A1 - Kirchgäßner, Christoph
T1 - Bestimmung von Referenzbereichen für die Schilddrüsenhormonparameter TSH, fT3 und fT4 bei Neugeborenen, Kindern und Jugendlichen
T1 - Reference values of thyroid hormones TSH, fT3 and fT4 for newborns, children and teenagers
N2 - Neubestimmung der Referenzbereiche für die Schilddrüsenhormonparameter TSH, fT3 und fT4 für Kinder von der Geburt bis zum 18. Lebensjahr mittels Immulite Immunoassay.
N2 - Creation of new reference values for thyroid hormones TSH, fT3 and fT4 for children using the Immulite immunoassay
KW - Schilddrüse
KW - Thyreotropin
KW - Thyroxin
KW - Normalwert
KW - fT3
KW - fT4
KW - Immulite
KW - Immunoassay
KW - Referenzbereiche
KW - reference values
KW - thyroid
KW - TSH
KW - fT3
KW - fT4
Y1 - 2010
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-54090
ER -
TY - THES
A1 - Neumann, Sabrina
T1 - Beta-Strahlenexposition der Finger bei der Radiosynoviorthese
T1 - Beta-Radioexposure to fingertips during radiosynovectomy
N2 - There are few, but worrisome, data available on fingertip
radiation exposure of medical personnel during
radiosynovectomy (RSV). To reduce radiation exposure, we
performed a dedicated application procedure. This report
summarizes the acquired skin equivalent dose [Hp(0.07)] of
the personnel involved in the preparation and administration
of the three RSV !-emitters 90Y, 186Re and 169Er. Over a
period of 3 years, 547 joints in 368 patients were treated
with 52 421MBq of the aforementioned three radionuclides.
The Hp(0.07) was recorded with thermoluminescence
dosimeters worn on the dominant index fingertip and was
analysed monthly. Eight staff members were exposed to an
Hp(0.07) of 492 mSv. The cumulative dose was less than 10
μSv/MBq. The dose per person was 1.1 μSv/MBq in
physicians and up to 4.5 μSv/MBq in technicians. The
accumulated personal Hp(0.07) during RSV was far below
the regulatory limit and published data.
N2 - Die Radiosynoviorthese ist ein etabliertes Therapieverfahren zur Behandlung der Synovialitis.
Da bei der Radiosynoviorthese die Handhabung von radioaktiven β-Strahlern wie Yttrium, Rhenium und Erbium notwendig ist, sind bestimmte Schutzmaßnahmen einzuhalten. Zum Schutze des Patienten wurden Leitlinien aufgestellt, um die Strahlenbelastung so gering wie möglich zu halten. Die Exposition der bei der Vorbereitung und Applikation beteiligten Ärzte, Radiopharmazeuten sowie beteiligten Krankenschwestern bietet Raum für weitere Verbesserungen.
Eine Untersuchung des Bundesamt für Strahlenschutz dokumentiert höchst bedenkliche Zahlen, für die β-Ortsdosimetrie, die die zulässige Jahresdosis um ein Vielfaches überschreiten können.
Die Einführung von sogenannten Thermolumineszensdetektoren, getragen als Ringdosimeter an den Grundgelenken der Zeigefinger, sollen realistische Expositionswerte aufzeichnen und somit eine Kontrolle der Dosis ermöglichen. Diese TLD’s sind mit der Markierung „RSO“ gekennzeichnet und werden nur bei der Arbeit mit den radioaktiven Substanzen getragen. Die monatliche Auswertung dokumentiert die Strahlenexposition der beteiligten Personen.
In verschiedenen Studien wurden Methoden zur Minimierung der Strahlenexposition getestet. Sie führten zu dem Ergebnis, dass die Abschirmung mit Acrylglas, die Abstandshaltung durch langschenklige Zangen sowie das Tragen von Nitril-Handschuhen am effektivsten zu einer Verringerung der Expositionswerte beitragen.
Ziel dieser retrospektiven Auswertung von Daten aus drei Jahren war es, die Effektivität der an der Klinik und Poliklinik für Nuklearmedizin in Würzburg praktizierten Strahlenschutzmaßnahmen zu untersuchen.
Über einen Zeitraum von drei Jahren wurden 547 Gelenke in 368 Patienten mit 52.421 MBq, der drei Radionuklide 169Er, 186Re und 90Y behandelt. Die Oberflächenpersonendosis Hp(0,07) wurde mittels Fingerringdosimeter aufgezeichnet.
Die acht an der Radiosynoviorthese beteiligten Personen erhielten eine kumulative Hautdosis Hp(0,07) von 498 mSv. Die kumulative Dosis pro Aktivität betrug somit weniger als 10 mSv/Bq. Sie lag pro Arzt bei 1,1 μSv/MBq und pro MTA bei bis zu 4,5 μSv/MBq.
Die akkumulierte Hautdosis Hp (0,07) während der Radiosynoviorthese war somit weitaus geringer im Vergleich zu den gesetzlichen Vorgaben und den zur Verfügung stehenden publizierten Daten.
KW - Radiosynoviorthese
KW - Beta-Strahlenexposition
KW - Yttrium
KW - Rhenium
KW - Erbium
KW - radiosynovectomy
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154271
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Hayakawa, Nobuyuki
A1 - Arias-Loza, Paula-Anah
A1 - Wakabayashi, Hiroshi
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Pelzer, Theo
A1 - Higuchi, Takahiro
T1 - Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell
T2 - Nuklearmedizin
N2 - Einleitung: Die linksventrikuläre diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann.
Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG über die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikuläre Ejektionsfraktion (EF) und die Peak Füllrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Größe des Rattenherzes angepasst wurde.
Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, bestätigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.).
Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der frühen diabetischen Kardiomyopathie nachgewiesen werden.
KW - Positronen-Emissions-Tomografie
KW - Diabetes
KW - diabetische Kardiomyopathie
KW - Positronen-Emissions-Tomografie
KW - PET
KW - EKG
KW - ECG
KW - ECG-gated
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161396
UR - http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
SN - 0029-5566
N1 - This article is not an exact copy of the original published article in Nuklearmedizin.
The definitive publisher-authenticated version of „Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell. Nuklearmedizin 2017; 56 (Abstract Nr.: V119).“ is available online at http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
VL - 56
IS - 2
PB - Schattauer Verlag
ER -
TY - THES
A1 - Heinrich, Marieke
T1 - Bildgebung des Prostatakarzinoms im PSMA-PET/CT: Die halbautomatische Quantifizierung des Tumorvolumens zeigt (noch) keine verbesserte Prädiktion des Krankheitsverlaufs
T1 - Imaging of prostate cancer in PSMA-PET/CT: Semi-automatic quantification of tumor volume does not (yet) show any improved prediction of disease progression
N2 - Die molekularen Parameter PSMA-TV und TL-PSMA im 68Ga-PSMA PET/CT leiten sich ab von MTV und TLG im FDG PET/CT. Mit der vorliegenden Arbeit wurden die Grenzen neuer Autosegmentierungsprogramme durch eine maximale Belastung mit großen Tumorvolumina von Patienten unter taxanbasierter Chemotherapie ausgelotet. Die Programme Syngo.via und FIJI kamen zu vergleichbaren Ergebnissen. Patienten mit einem Gleason Score von 8-10 zeigten unter Therapie eine signifikante Zunahme des PSMA-TV und TL-PSMA im Gegensatz zu Patienten mit Gleason Score 6-7b. Ein hoher PSA-Wert korrelierte zu allen Zeitpunkten signifikant mit einem hohen PSMA-TV und TL-PSMA, ebenso korrelierte ein steigender PSA-Wert signifikant mit steigenden Werten in PSMA-TV und TL-PSMA. Patienten mit einem biochemischen Progress und einem Progress nach modifiziertem PERCIST zeigten vor Therapie ein signifikant höheres PSMA-TV und TL-PSMA als Patienten ohne Progress und unter Therapie eine signifikante Zunahme des PSMA-TV und TL-PSMA im Vergleich zu Patienten ohne Progress. Eine Einteilung des Therapieansprechens aller Patienten in CR, PR, SD und PD nach PSMA-TV, TL-PSMA, PSA-Wert und modifiziertem PERCIST stimmte nicht in allen Patienten überein. Ein signifikant kürzeres Gesamtüberleben zeigten lediglich Patienten mit einem nach dem PSA-Wert definiertem Progress. Im praktischen Vergleich der beiden Programme benötigte Syngo.via für eine komplette Segmentierung signifikant mehr Zeit als FIJI, vor allem da der Wechsel von VOI zu VOI signifikant länger dauerte. Unabhängig vom Autosegmentierungsprogramm dauerte eine komplette Segmentierung länger, je größer das PSMA-TV und das TL-PSMA war, je mehr VOIs das Programm automatisch setzte und je mehr VOIs manuell gelöscht und neu gesetzt wurden. In der Gesamtschau bieten PSMA-TV und TL-PSMA in Kombination mit den sich schnell weiterentwickelnden Autosegmentierungs-Programmen die Möglichkeit, auch sehr hohe Tumorlasten des PCas objektiv und vergleichbar zu beschreiben.
N2 - The molecular parameters PSMA-TV and TL-PSMA in 68Ga-PSMA PET/CT are derived from MTV and TLG in FDG PET/CT. The present work explored the limits of new autosegmentation programs with large tumor volumes from patients receiving taxane-based chemotherapy. The programs Syngo.via and FIJI achieved comparable results. Patients with a Gleason score of 8-10 showed a significant increase in PSMA-TV and TL-PSMA during therapy in contrast to patients with Gleason scores 6-7b. A high PSA value was significantly correlated with a high PSMA-TV and TL-PSMA at all time points, and an increasing PSA value was also significantly correlated with increasing values in PSMA-TV and TL-PSMA. Patients with biochemical progression and progression according to modified PERCIST showed a significantly higher PSMA-TV and TL-PSMA before therapy than patients without progression and a significant increase in PSMA-TV and TL-PSMA during therapy compared to patients without progression. A classification of therapy response in all patients into CR, PR, SD and PD based on PSMA-TV, TL-PSMA, PSA value and modified PERCIST was not consistent in all patients. Only patients with progression defined by the PSA value showed a significantly shorter overall survival. In a practical comparison of the two programs, Syngo.via required significantly more time for complete segmentation than FIJI, especially since switching from VOI to VOI took significantly longer. Regardless of the auto-segmentation program, complete segmentation took longer as the PSMA-TV and TL-PSMA increased, and as the program automatically set more VOIs and more VOIs were manually deleted and reset. Overall, PSMA-TV and TL-PSMA in combination with the rapidly developing auto-segmentation programs offer the possibility of objectively and comparably describing even very high PCa tumor burdens.
KW - Hormonrefraktärer Prostatakrebs
KW - Positronen-Emissions-Tomografie
KW - Chemotherapie
KW - Tumorvolumen
Y1 - 2024
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359684
ER -
TY - JOUR
A1 - Eberlein, Uta
A1 - Bröer, Jörn Hendrik
A1 - Vandevoorde, Charlot
A1 - Santos, Paula
A1 - Bardiès, Manuel
A1 - Bacher, Klaus
A1 - Nosske, Dietmar
A1 - Lassmann, Michael
T1 - Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Purpose
The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals.
Methods
A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting.
Results
Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago.
Conclusion
It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained.
KW - Dosimetry
KW - Biokinetics
KW - Diagnostic radiopharmaceuticals
KW - Effective dose
Y1 - 2011
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133846
VL - 38
IS - 12
ER -
TY - JOUR
A1 - Soares Machado, J.
A1 - Tran-Gia, J.
A1 - Schlögl, S.
A1 - Buck, A. K.
A1 - Lassmann, M.
T1 - Biokinetics, dosimetry, and radiation risk in infants after \(^{99m}\)Tc-MAG3 scans
JF - EJNMMI Research
N2 - Background:
Renal scans are among the most frequent exams performed on infants and toddlers. Due to the young age, this patient group can be classified as a high-risk group with a higher probability for developing stochastic radiation effects compared to adults. As there are only limited data on biokinetics and dosimetry in this patient group, the aim of this study was to reassess the dosimetry and the associated radiation risk for infants undergoing \(^{99m}\)Tc-MAG3 renal scans based on a retrospective analysis of existing patient data. Consecutive data were collected from 20 patients younger than 20 months (14 males; 6 females) with normal renal function undergoing \(^{99m}\)Tc-MAG3 scans. To estimate the patient-specific organ activity, a retrospective calibration was performed based on a set of two 3D-printed infant kidneys filled with known activities. Both phantoms were scanned at different positions along the anteroposterior axis inside a water phantom, providing depth- and size-dependent attenuation correction factors for planar imaging. Time-activity curves were determined by drawing kidney, bladder, and whole-body regions-of-interest for each patient, and subsequently applying the calibration factor for conversion of counts to activity. Patient-specific time-integrated activity coefficients were obtained by integrating the organ-specific time-activity curves. Absorbed and effective dose coefficients for each patient were assessed with OLINDA/EXM for the provided newborn and 1-year-old model. The risk estimation was performed individually for each of the 20 patients with the NCI Radiation Risk Assessment Tool.
Results:
The mean age of the patients was 7.0 ± 4.5 months, with a weight between 5 and 12 kg and a body size between 60 and 89 cm. The injected activities ranged from 12 to 24 MBq of \(^{99m}\)Tc-MAG3. The patients' organ-specific mean absorbed dose coefficients were 0.04 ± 0.03 mGy/MBq for the kidneys and 0.27 ± 0.24 mGy/MBq for the bladder. The mean effective dose coefficient was 0.02 ± 0.02 mSv/MBq. Based on the dosimetry results, an evaluation of the excess lifetime risk for the development of radiation-induced cancer showed that the group of newborns has a risk of 16.8 per 100,000 persons, which is about 12% higher in comparison with the 1-year-old group with 14.7 per 100,000 persons (all values are given as mean plus/minus one standard deviation except otherwise specified).
Conclusion:
In this study, we retrospectively derived new data on biokinetics and dosimetry for infants with normal kidney function after undergoing renal scans with \(^{99m}\)Tc-MAG3. In addition, we analyzed the associated age- and gender-specific excess lifetime risk due to ionizing radiation. The radiation-associated stochastic risk increases with the organ doses, taking age- and gender-specific influences into account. Overall, the lifetime radiation risk associated with the \(^{99m}\)Tc-MAG3 scans is very low in comparison to the general population risk for developing cancer.
KW - \(^{99m}\)Tc-MAG3
KW - absorbed dose
KW - biokinetics
KW - dosimetry
KW - pediatric patients
KW - risk assessment
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175582
VL - 8
IS - 10
ER -
TY - JOUR
A1 - Isaias, Ioannis U.
A1 - Brumberg, Joachim
A1 - Pozzi, Nicoló G.
A1 - Palmisano, Chiara
A1 - Canessa, Andrea
A1 - Marotta, Giogio
A1 - Volkmann, Jens
A1 - Pezzoli, Gianni
T1 - Brain metabolic alterations herald falls in patients with Parkinson's disease
JF - Annals of Clinical and Translational Neurology
N2 - Pathophysiological understanding of gait and balance disorders in Parkinson’s disease is insufficient and late recognition of fall risk limits efficacious followup to prevent or delay falls. We show a distinctive reduction of glucose metabolism in the left posterior parietal cortex, with increased metabolic activity in the cerebellum, in parkinsonian patients 6–8 months before their first fall episode. Falls in Parkinson’s disease may arise from altered cortical processing of body spatial orientation, possibly predicted by abnormal cortical metabolism.
KW - Parkionson's disease
KW - brain metabolic alterations
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235982
VL - 7
IS - 4
ER -
TY - JOUR
A1 - Reiners, Christoph
A1 - Schneider, Rita
A1 - Platonova, Tamara
A1 - Fridman, Mikhail
A1 - Malzahn, Uwe
A1 - Mäder, Uwe
A1 - Vrachimis, Alexis
A1 - Bogdanova, Tatiana
A1 - Krajewska, Jolanta
A1 - Elisei, Rossella
A1 - Vaisman, Fernanda
A1 - Mihailovic, Jasna
A1 - Costa, Gracinda
A1 - Drozd, Valentina
T1 - Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey
JF - Frontiers in Endocrinology
N2 - Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.”
KW - differentiated thyroid carcinoma
KW - radioiodine therapy
KW - iodine-131
KW - long-term complications
KW - young females
KW - childhood and adolescence
KW - second primary malignancy
KW - breast cancer
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207766
SN - 1664-2392
VL - 11
ER -
TY - JOUR
A1 - Eberlein, Uta
A1 - Peper, Michel
A1 - Fernández, Maria
A1 - Lassmann, Michael
A1 - Scherthan, Harry
T1 - Calibration of the \(\gamma\)-H2AX DNA double strand break focus assay for internal radiation exposure of blood lymphocytes
JF - PLoS ONE
N2 - DNA double strand break (DSB) formation induced by ionizing radiation exposure is indicated by the DSB biomarkers \(\gamma\)-H2AX and 53BP1. Knowledge about DSB foci formation in-vitro after internal irradiation of whole blood samples with radionuclides in solution will help us to gain detailed insights about dose-response relationships in patients after molecular radiotherapy (MRT). Therefore, we studied the induction of radiation-induced co-localizing \(\gamma\)-H2AX and 53BP1 foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per cell values with the in-vitro absorbed doses to the blood for the two most frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers were analyzed. For each experiment several vials containing a mixture of whole blood and radioactive solutions with different concentrations of isotonic NaCl-diluted radionuclides with known activities were prepared. Leukocytes were recovered by density centrifugation after incubation and constant blending for 1 h at 37°C. After ethanol fixation they were subjected to two-color immunofluorescence staining and the average frequencies of the co-localizing \(\gamma\)-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope equipped with a red/green double band pass filter. The exact activity was determined in parallel in each blood sample by calibrated germanium detector measurements. The absorbed dose rates to the blood per nuclear disintegrations occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A linear relationship was found between the number of DSB-marking foci/nucleus and the absorbed dose to the blood for both radionuclides studied. There were only minor nuclide-specific intra-and inter-subject deviations.
KW - in vivo formation
KW - chromatin mobility
KW - phosphorylation
KW - repair
KW - 53BP1
KW - damage
KW - radioiodine therapy
KW - thyroid cancer
KW - histone H2AX
KW - dose response
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148697
VL - 10
IS - 4
ER -
TY - THES
A1 - Janßen, Jan Paul
T1 - Capabilities of a multi-pinhole SPECT system with two stationary detectors for in vivo imaging in rodents
T1 - Leistungsfähigkeit eines Multi-Pinhole SPECT-Systems mit zwei stationären Detektoren zur In-vivo-Bildgebung in Nagetiermodellen
N2 - Molecular imaging of rats is of great importance for basic and translational research. As a powerful tool in nuclear medicine, SPECT can be used to visualize specific functional processes in the body, such as myocardial perfusion or bone metabolism. Typical applications in laboratory animals are imaging diagnostics or the development of new tracers for clinical use. Innovations have enabled resolutions of up to a quarter of a millimeter with acceptable sensitivity. These advances have recently led to significantly more interest in SPECT both clinically and preclinically.
The objective of this thesis was to evaluate the performance of the new U-SPECT5/CT E-Class by MILabs with a dedicated ultra-high resolution multi-pinhole collimator for rats and its potential for in vivo imaging of rats. The unique features of the U-SPECT are the large stationary detectors and the new iterative reconstruction algorithm. In addition, compared to the conventional system, the "E-Class" uses only two detectors instead of three.
First, the sensitivity, maximum resolution, and uniformity were determined as performance parameters. Thereafter, CNRs for different activity levels comparable to those of typical in vivo activities were examined. Finally, two example protocols were carried out for imaging with 99mTc-MIBI and 99mTc-HMDP in healthy rats to evaluate the in vivo capabilities. For this purpose, CNR calculations and an image quality assessment were performed. The focus was on image quality as a function of scan time and post-reconstruction filter across a wide range of realistically achievable in vivo conditions.
Performance was reasonable compared to other systems in the literature, with a sensitivity of 567 cps/MBq, a maximum resolution of 1.20 mm, and a uniformity of 55.5%. At the lower activities, resolution in phantom studies decreased to ≥1.80 mm while maintaining good image quality. High-quality bone and myocardial perfusion SPECTs were obtained in rats with a resolution of ≥1.80 mm and ≥2.20 mm, respectively. Although limited sensitivity remains a weakness of SPECT, the U-SPECT5/CT E-Class with the UHR-RM collimator can achieve in vivo results of the highest standard despite the missing third detector. Currently, it is one of the best options for high-resolution radionuclide imaging in rats.
N2 - Die molekulare Bildgebung bei Ratten hat einen hohen Stellenwert in der Grundlagenforschung und der translationale Forschung. Dabei ist SPECT ein leistungsfähiges Instrument zur Visualisierung spezifischer funktioneller Prozesse im Körper, wie z. B. der Herzmuskeldurchblutung oder des Knochenstoffwechsels. Typische Anwendungsbereiche an Labortieren sind die bildgebende Diagnostik im Rahmen von Studien oder die Entwicklung neuer Tracer für den klinischen Einsatz. Durch Innovationen wurden Auflösungen von bis zu einem Viertelmillimeter bei akzeptabler Empfindlichkeit erreichbar. Diese Fortschritte haben in letzter Zeit zu einem deutlich gestiegenen Interesse an SPECT sowohl im klinischen als auch im präklinischen Bereich geführt.
Ziel dieser Arbeit war es, die Leistung des neuen U-SPECT5/CT E-Class von MILabs mit einem speziellen ultra-hochauflösenden Multi-Pinhole-Kollimator für Ratten und das Potenzial für die In-vivo-Bildgebung bei Ratten zu untersuchen. Dabei sind die Besonderheiten des U-SPECTs die großen stationären Detektoren und der neue iterative Rekonstruktionsalgorithmus. Außerdem verfügt die von uns verwendete „E-Klasse“ im Vergleich zum konventionellen System nur über zwei statt drei Detektoren.
Zunächst wurden die Sensitivität, die maximale Ortsauflösung und die Homogenität als Leistungsparameter bestimmt. Anschließend wurde das Kontrast-Rausch-Verhältnis für verschiedene Aktivitätsniveaus, die mit denen typischer In-vivo-Studien vergleichbar sind, untersucht. Schließlich wurden zwei Beispielprotokolle für die Bildgebung mit 99mTc-MIBI und 99mTc-HMDP bei gesunden Ratten durchgeführt, um die In-vivo-Kapazitäten zu erfassen. Zur Bewertung wurden eine Kontrast-Rausch-Analyse und eine Bildqualitätsumfrage genutzt. Der Schwerpunkt lag dabei auf der Bildqualität in Abhängigkeit von der Scanzeit sowie dem Postrekonstruktionsfilters für ein breites Spektrum realistisch erreichbarer In-vivo-Bedingungen.
Die Leistung war mit einer Sensitivität von 567 cps/MBq, einer maximalen Ortsauflösung von 1,20 mm und einer Homogenität von 55,5% mit anderen in der Literatur beschriebenen Systemen vergleichbar. Bei niedrigeren Aktivitäten verringerte sich die Auflösung in Phantomstudien auf ≥1,80 mm bei gleichbleibend guter Bildqualität. Es wurden hochqualitative Knochen- und Myokardperfusions-SPECTs mit einer Auflösung von ≥1,80 mm bzw. ≥2,20 mm bei Ratten erzielt. Obwohl die begrenzte Empfindlichkeit nach wie vor eine Schwäche der SPECT ist, kann das U-SPECT5/CT E-Class mit dem UHR-RM-Kollimator, trotz des fehlenden dritten Detektors, In-vivo-Ergebnisse auf höchstem Niveau erzielen. Es ist derzeit eine der besten Optionen für die hochauflösende Radionuklid-Bildgebung bei Ratten.
KW - SPECT
KW - Molekulare Bildgebung
KW - Rodents
KW - Image Quality
KW - SPECT/CT
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328608
ER -
TY - JOUR
A1 - Janssen, Jan P.
A1 - Hoffmann, Jan V.
A1 - Kanno, Takayuki
A1 - Nose, Naoko
A1 - Grunz, Jan-Peter
A1 - Onoguchi, Masahisa
A1 - Chen, Xinyu
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
T1 - Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging
JF - Scientific Reports
N2 - We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available \(^{99m}\)Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with \(^{99m}\)Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [\(^{99m}\)TcTc-MIBI or similar to 150 MBq [\(^{99m}\)Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.
KW - small animal SPECT
KW - HMDP hydroxymethylene diphosphonate
KW - skeletal
KW - quality
KW - scanner
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230616
VL - 10
ER -
TY - JOUR
A1 - Tolstik, Elen
A1 - Ali, Nairveen
A1 - Guo, Shuxia
A1 - Ebersbach, Paul
A1 - Möllmann, Dorothe
A1 - Arias-Loza, Paula
A1 - Dierks, Johann
A1 - Schuler, Irina
A1 - Freier, Erik
A1 - Debus, Jörg
A1 - Baba, Hideo A.
A1 - Nordbeck, Peter
A1 - Bocklitz, Thomas
A1 - Lorenz, Kristina
T1 - CARS imaging advances early diagnosis of cardiac manifestation of Fabry disease
JF - International Journal of Molecular Sciences
N2 - Vibrational spectroscopy can detect characteristic biomolecular signatures and thus has the potential to support diagnostics. Fabry disease (FD) is a lipid disorder disease that leads to accumulations of globotriaosylceramide in different organs, including the heart, which is particularly critical for the patient’s prognosis. Effective treatment options are available if initiated at early disease stages, but many patients are late- or under-diagnosed. Since Coherent anti-Stokes Raman (CARS) imaging has a high sensitivity for lipid/protein shifts, we applied CARS as a diagnostic tool to assess cardiac FD manifestation in an FD mouse model. CARS measurements combined with multivariate data analysis, including image preprocessing followed by image clustering and data-driven modeling, allowed for differentiation between FD and control groups. Indeed, CARS identified shifts of lipid/protein content between the two groups in cardiac tissue visually and by subsequent automated bioinformatic discrimination with a mean sensitivity of 90–96%. Of note, this genotype differentiation was successful at a very early time point during disease development when only kidneys are visibly affected by globotriaosylceramide depositions. Altogether, the sensitivity of CARS combined with multivariate analysis allows reliable diagnostic support of early FD organ manifestation and may thus improve diagnosis, prognosis, and possibly therapeutic monitoring of FD.
KW - coherent anti-Stokes Raman scattering (CARS) microscopy
KW - Raman micro-spectroscopy
KW - cardiovascular diseases
KW - Fabry Disease (FD)
KW - Gb3 and lyso-Gb3 biomarkers
KW - multivariate data analysis
KW - immunohistochemistry
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284427
SN - 1422-0067
VL - 23
IS - 10
ER -
TY - JOUR
A1 - Lenschow, Christina
A1 - Fuss, Carmina Teresa
A1 - Kircher, Stefan
A1 - Buck, Andreas
A1 - Kickuth, Ralph
A1 - Reibetanz, Joachim
A1 - Wiegering, Armin
A1 - Stenzinger, Albrecht
A1 - Hübschmann, Daniel
A1 - Germer, Christoph Thomas
A1 - Fassnacht, Martin
A1 - Fröhling, Stefan
A1 - Schlegel, Nicolas
A1 - Kroiss, Matthias
T1 - Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management
JF - Frontiers in Endocrinology
N2 - Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
KW - parathyroid carcinoma
KW - abdominal lymph node metastases
KW - molecular diagnostics
KW - repeated surgery
KW - [18F]FDG-PET-CT
KW - immune check inhibitor
KW - pembrolizumab
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233362
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Detomas, Mario
A1 - Altieri, Barbara
A1 - Schlötelburg, Wiebke
A1 - Appenzeller, Silke
A1 - Schlaffer, Sven
A1 - Coras, Roland
A1 - Schirbel, Andreas
A1 - Wild, Vanessa
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
A1 - Fassnacht, Martin
A1 - Deutschbein, Timo
T1 - Case Report: Consecutive Adrenal Cushing’s Syndrome and Cushing’s Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations
JF - Frontiers in Endocrinology
N2 - The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.
KW - Cushing’s syndrome
KW - Cushing’s disease
KW - hypercortisolism
KW - glucocorticoid excess
KW - USP8
KW - CTNNB1
KW - NR3C1
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244596
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Mihatsch, Patrick W.
A1 - Beissert, Matthias
A1 - Pomper, Martin G.
A1 - Bley, Thorsten A.
A1 - Seitz, Anna K.
A1 - Kübler, Hubert
A1 - Buck, Andreas K.
A1 - Rowe, Steven P.
A1 - Serfling, Sebastian E.
A1 - Hartrampf, Philipp E.
A1 - Werner, Rudolf A.
T1 - Changing threshold-based segmentation has no relevant impact on semi-quantification in the context of structured reporting for PSMA-PET/CT
JF - Cancers
N2 - Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.
KW - \(^{18}\)F-PSMA-1007
KW - PET/CT
KW - staging
KW - prostate cancer
KW - standardized reporting system
KW - PSMA-RADS
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254782
SN - 2072-6694
VL - 14
IS - 2
ER -
TY - JOUR
A1 - Brumberg, Joachim
A1 - Küsters, Sebastian
A1 - Al-Momani, Ehab
A1 - Marotta, Giorgio
A1 - Cosgrove, Kelly P.
A1 - van Dyck, Christopher H.
A1 - Herrmann, Ken
A1 - Homola, György A.
A1 - Pezzoli, Gianni
A1 - Buck, Andreas K.
A1 - Volkmann, Jens
A1 - Samnick, Samuel
A1 - Isaias, Ioannis U.
T1 - Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study
JF - Annals of Clinical and Translational Neurology
N2 - Objective: To investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.
Methods: This study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[\(^{123}\)I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [\(^{123}\)I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[\(^{18}\)F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.
Results: Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.
Interpretation: Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.
KW - levodopa-induced dyskinesia
KW - cholinergic activity
KW - Parkinson’s disease
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170406
VL - 4
IS - 9
ER -
TY - THES
A1 - Blasl, Christiana
T1 - Chromatografischer Nachweis endogen radioiodierter Verbindungen im Urin von Patienten mit differenziertem Schilddrüsenkarzinom nach Iod-131-Ganzkörperszintigrafie
T1 - Chromatographic identification of endogenously radioiodinated thyroid products in urine of patients with differentiated thyroid carcinoma after I-131-whole-body-scintigraphy
N2 - Der Follow-UP von Patienten mit differenziertem Schilddrüsenkarzinom (DTC) wird konventionell mit I-131-Ganzkörperzintigrafie (GKS) und Bestimmung des Serumthyreoglobulins (hTg) durchgeführt. Wegen der Inzidenz von 15%-20% diskordanter Resultate entwickelte Bianchi et al. (J Nucl Med 1993; 34: 2032-2037) die Serumchromatografie von endogen radioiodiertem Triiodthyronin (L-T3) und Thyroxin (L-T4) bei Patienten mit DTC nach oraler Applikation von I-131. Da im Rahmen des Iodstoffwechsels auch radioiodierte Verbindungen im Urin erscheinen, versuchten wir eine Urinchromatografiemethode zu entwickeln, basierend auf der Annahme, dass ein pathologischer I-131-Uptake, wenngleich zu niedrig um im GKS erkannt zu werden, gleichwohl über endogen iodierte Schilddrüsenprodukte im Urin nachgewiesen werden kann. In der Urinchromatografie konnten die Ergebnisse der Serumchromatografie nicht erreicht werden.
N2 - Patients with DTC are conventionally followed up with serial I-131- whole-body-scintigraphy (WBS) and serum thyroglobulin (hTg) measurements. Given the 15%-20% incidence of discordant results Bianchi et al. (J Nucl Med 1993; 34: 2032-2037) established the serum chromatographic identification of endogenously radioiodinated thyroid hormones after I-131-WBS in the follow-up of patients with DTC. We tried to establish an urine chromatographic method of patients with DTC, based on the assumption that I-131-uptake, though too low to be detected by I-131-WBS, could be assayed in urine as endogenously labeled and excreted thyroid products. The urine chromatographic method did not show the good results of the serum chromatographic method.
KW - Differenziertes Schilddrüsenkarzinom
KW - I-131-Ganzkörperzintigrafie
KW - Thyreoglobulin (hTg)
KW - Urinchromatografie
KW - Serumchromatografie
KW - differentiated thyroid carcinoma
KW - I-131-whole-body-scintigraphy
KW - thyroglobulin (hTg)
KW - urine chromatographic method
KW - serum chromatographic method
Y1 - 2004
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-12726
ER -
TY - JOUR
A1 - Da Vià, Matteo Claudio
A1 - Solimando, Antonio Giovanni
A1 - Garitano-Trojaola, Andoni
A1 - Barrio, Santiago
A1 - Munawar, Umair
A1 - Strifler, Susanne
A1 - Haertle, Larissa
A1 - Rhodes, Nadine
A1 - Vogt, Cornelia
A1 - Lapa, Constantin
A1 - Beilhack, Andreas
A1 - Rasche, Leo
A1 - Einsele, Hermann
A1 - Kortüm, K. Martin
T1 - CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF‐MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement
JF - The Oncologist
N2 - Combined MEK‐BRAF inhibition is a well‐established treatment strategy in BRAF‐mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF‐MEK inhibitor treatment are unavailable.
Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high‐risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.
KW - Multiple myeloma
KW - Extramedullary disease
KW - Capicua transcriptional repressor
KW - Drug resistance
KW - BRAF mutation
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219549
VL - 25
IS - 2
ER -
TY - JOUR
A1 - Reiners, Christoph
T1 - Clinical Experiences with Radiation Induced Thyroid Cancer after Chernobyl
N2 - The risk of developing thyroid cancer increases considerably after exposure to external or internal radiation, especially in children below the age of 10. After the Chernobyl reactor accident, the yearly incidence of childhood thyroid cancer in Belarus increased to approximately 40 per 1.000.000 in girls and to roughly 20 per 1.000.000 in boys compared to approximately 0.5 cases per 1.000.000 prior to the accident. Typically, young children with thyroid cancer after radiation exposure present in ≈95% of the cases as papillary cancers, in ≈50% as invasive tumors growing outside the thyroid capsule, in ≈65% with lymph node metastases and in ≈15% with distant metastases. A joint Belarusian-German project starting in April 1993 that combined treatment with surgery and radioiodine was organized in 237 selected children from Belarus who were exposed to the Chernobyl fallout and had advanced stages of thyroid cancer. The study group included 141 girls and 96 boys. Their median age at the time of the accident was 1.7 years; whereas the median age at the time of diagnosis was 12.4 years. With the exception of two cases with follicular histology, the majority of the patients had been diagnosed with papillary thyroid cancers. In 63%, the tumor had grown outside the thyroid capsule and invaded the tissue of the neck (pT4). Nearly all of the selected cases (96%) showed-up with lymph node metastases (pN1) and 43% of the patients with distant metastases mainly to the lungs (pM1). In 58% of the children, complete remissions of thyroid cancer could be achieved until December 31st 2010 and in 34% of the children, stable partial remissions; in the remaining 8% of the patients, partial remissions were observed. The risk of radiation-induced thyroid cancer increased considerably in children and adolescents who were affected by the Chernobyl reactor accident. In spite of the fact, that thyroid cancers in young children seem to behave more aggressively than in older patients, the results of combined treatment with thyroidectomy, radioiodine therapy and thyroid hormone replacement are excellent.
KW - Chernobyl
KW - Chernobyl
KW - children
KW - thyroid cancer
KW - advanced stages
KW - treatment
KW - prognosis
Y1 - 2011
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75475
ER -
TY - JOUR
A1 - Herrmann, Ken
A1 - Wieder, Hinrich A.
A1 - Lassmann, Michael
A1 - Allen-Auerbach, Martin S.
A1 - Czernin, Johannes
T1 - Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters
N2 - Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available. In contrast to β-emitters, 223Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity. The α emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the 223Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of 223Radium was favourable. Since May 2013, 223Radium dichloride (Xofigo®) is approved by the US Food and Drug Administration.
Core tip: The incidence rate of prostate cancer worldwide is high. Ninety percent of patients dying of prostate cancer have bone metastases with varying symptoms which are significantly impairing their quality of life. 223Radium is the first therapeutic that results in a survival benefit for patients with bone metastatic, castrate resistant prostate cancer. 223Radium was also associated with low myelosuppression rates and fewer adverse events.This article provides an overview of the pre-clinical and clinical trials with 223Radium.
KW - bone-targeting radiopharmaceuticals
KW - Radium
KW - alpha-emitters
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113014
ER -
TY - JOUR
A1 - Israel, Ina
A1 - Ohsiek, Andrea
A1 - Al-Momani, Ehab
A1 - Albert-Weissenberger, Christiane
A1 - Stetter, Christian
A1 - Mencl, Stine
A1 - Buck, Andreas K.
A1 - Kleinschnitz, Christoph
A1 - Samnick, Samuel
A1 - Sirén, Anna-Leena
T1 - Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice
JF - Journal of Neuroinflammation
N2 - Background
Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry.
Methods
A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo μPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [\(^{18}\)F]DPA-714 was performed on day 1, 7, and 16 and [\(^{18}\)F]FDG-μPET imaging for energy metabolism on days 2–5 after trauma using freshly synthesized radiotracers. Immediately after [\(^{18}\)F]DPA-714-μPET imaging on days 7 and 16, cellular identity of the [\(^{18}\)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1.
Results
Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [\(^{18}\)F]DPA-714-μPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [\(^{18}\)F]FDG uptake on days 2–5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [\(^{18}\)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [\(^{18}\)F]DPA-714 was not increased in autoradiography or in μPET imaging.
Conclusions
[\(^{18}\)F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI.
KW - neuroinflammation
KW - TBI
KW - immunohistochemistry
KW - weight drop
KW - PET
KW - diffuse
KW - focal
KW - TSPO
KW - autoradiography
KW - IBA-1
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146606
VL - 13
IS - 140
ER -
TY - JOUR
A1 - Lassmann, Michael
A1 - Eberlein, Uta
T1 - Comparing absorbed doses and radiation risk of the α-emitting bone-seekers [\(^{223}\)Ra]RaCl\(_2\) and [\(^{224}\)Ra]RaCl\(_2\)
JF - Frontiers in Medicine
N2 - [\(^{223}\)Ra]RaCl\(_2\) and [\(^{224}\)Ra]RaCl\(_2\) are bone seekers, emitting high LET, and short range (< 100 μm) alpha-particles. Both radionuclides show similar decay properties; the total alpha energies are comparable (\(^{223}\)Ra: ≈28 MeV, \(^{224}\)Ra: ≈26 MeV). [\(^{224}\)Ra]RaCl\(_2\) has been used from the mid-1940s until 1990 for treating different bone and joint diseases with activities of up to approximately 50 MBq [\(^{224}\)Ra]RaCl\(_2\). In 2013 [\(^{223}\)Ra]RaCl\(_2\) obtained marketing authorization by the FDA and by the European Union for the treatment of metastatic prostate cancer with an activity to administer of 0.055 MBq per kg body weight for six cycles. For intravenous injections in humans a model calculation using the biokinetic model of ICRP67 shows a ratio of organ absorbed dose coefficients (\(^{224}\)Ra:\(^{223}\)Ra) between 0.37 (liver) and 0.97 except for the kidneys (2.27) and blood (1.57). For the red marrow as primary organ-at-risk, the ratio is 0.57. The differences are mainly caused be the differing half-lives of the decay products of both radium isotopes. Both radionuclides show comparable DNA damage patterns in peripheral blood mononuclear cells after internal ex-vivo irradiation. Data on the long-term radiation-associated side effects are only available for treatment with [\(^{224}\)Ra]RaCl\(_2\). Two epidemiological studies followed two patient groups treated with [\(^{224}\)Ra]RaCl\(_2\) for more than 25 years. One of them was the “Spiess study”, a cohort of 899 juvenile patients who received several injections of [\(^{224}\)Ra]RaCl\(_2\) with a mean specific activity of 0.66 MBq/kg. Another patient group of ankylosing spondylitis patients was treated with 10 repeated intravenous injections of [\(^{224}\)Ra]RaCl\(_2\), 1 MBq each, 1 week apart. In total 1,471 of these patients were followed-up in the “Wick study”. In both studies, an increased cancer mortality by leukemia and solid cancers was observed. Similar considerations on long-term effects likely apply to [\(^{223}\)Ra]RaCl\(_2\) as well since the biokinetics are similar and the absorbed doses in the same range. However, this increased risk will most likely not be observed due to the much shorter life expectancy of prostate cancer patients treated with [\(^{223}\)Ra]RaCl\(_2\).
KW - dosimetry
KW - biodosimetry
KW - 224Ra
KW - 223Ra
KW - epidemiology
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301509
SN - 2296-858X
VL - 9
ER -
TY - JOUR
A1 - Lisowski, Dominik
A1 - Hartrampf, Philipp E.
A1 - Hasenauer, Natalie
A1 - Nickl, Vera
A1 - Monoranu, Camelia-Maria
A1 - Tamihardja, Jörg
T1 - Complete loss of E-cadherin expression in a rare case of metastatic malignant meningioma: a case report
JF - BMC Neurology
N2 - Background
Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis.
Case presentation
We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment.
Conclusions
E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.
KW - beta-catenin
KW - E-cadherin
KW - meningioma
KW - peptide receptor radionuclide therapy (PRRT)
KW - radiotherapy
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357996
VL - 23
ER -
TY - JOUR
A1 - Schuhmann, Sarah
A1 - Eberlein, Uta
A1 - Müller, Jessica
A1 - Scherthan, Harry
A1 - Lassmann, Michael
T1 - Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224
JF - EJNMMI Research
N2 - Background:
Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes.
Results:
Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values.
Conclusions:
Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties.
KW - 53BP1
KW - DNA damage
KW - γ-H2AX
KW - biological dosimetry
KW - absorbed dose to the blood
KW - α-emitter
KW - Ra-224
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176593
VL - 8
IS - 77
ER -
TY - JOUR
A1 - Toyama, Yoshitaka
A1 - Werner, Rudolf A.
A1 - Ruiz-Bedoya, Camilo A.
A1 - Ordonez, Alvaro A.
A1 - Takase, Kei
A1 - Lapa, Constantin
A1 - Jain, Sanjay K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
T1 - Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
JF - Theranostics
N2 - In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C-11, Ga-68, and F-18 have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
KW - glomerular filtration rate
KW - renal
KW - kidney
KW - renal function
KW - positron emission tomography
KW - nephrology
KW - urology
KW - molecular imaging
KW - theranostics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260090
VL - 11
IS - 12
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Herrmann, Ken
A1 - Schirbel, Andreas
A1 - Hänscheid, Heribert
A1 - Lückerath, Katharina
A1 - Schottelius, Margret
A1 - Kircher, Malte
A1 - Werner, Rudolf A.
A1 - Schreder, Martin
A1 - Samnick, Samuel
A1 - Kropf, Saskia
A1 - Knop, Stefan
A1 - Buck, Andreas K.
A1 - Einsele, Hermann
A1 - Wester, Hans-Juergen
A1 - Kortüm, K. Martin
T1 - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
JF - Theranostics
N2 - C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM).
Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival.
ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive.
CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
KW - medicine
KW - multiple myeloma
KW - PET
KW - CXCR4
KW - theranostics
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095
VL - 7
IS - 6
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Kircher, Malte
A1 - Schirbel, Andreas
A1 - Wester, Hans-Jürgen
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
T1 - CXCR4-directed imaging in solid tumors
JF - Frontiers in Oncology
N2 - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms.
Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT.
Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions.
Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.
KW - CXCR4
KW - [68Ga]Pentixafor
KW - theranostics
KW - solid tumors
KW - chemokine receptor
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195678
SN - 2234-943X
VL - 9
IS - 770
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Lambertini, Alessandro
A1 - Hartrampf, Philipp E.
A1 - Higuchi, Takahiro
A1 - Serfling, Sebastian E.
A1 - Meybohm, Patrick
A1 - Schirbel, Andreas
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - No abstract available.
KW - CXCR4-targeting
KW - SARS-CoV-2
KW - COVID-19
KW - molecular imaging
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324619
VL - 50
IS - 1
ER -
TY - JOUR
A1 - Buck, Andreas K.
A1 - Serfling, Sebastian E.
A1 - Lindner, Thomas
A1 - Hänscheid, Heribert
A1 - Schirbel, Andreas
A1 - Hahner, Stefanie
A1 - Fassnacht, Martin
A1 - Einsele, Hermann
A1 - Werner, Rudolf A.
T1 - CXCR4-targeted theranostics in oncology
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
KW - CXCR4
KW - theranostics
KW - C-X-C motif chemokine receptor 4
KW - [68Ga]PentixaFor
KW - [177Lu]PentixaTher
KW - [90Y]PentixaTher
KW - endoradiotherapy
KW - adrenocortical carcinoma
KW - multiple myeloma
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324545
VL - 49
IS - 12
ER -
TY - THES
A1 - Kemmer, Luisa Diana
T1 - Darstellung von Inflammation in Atherosklerose mit dem CXCR4-gerichteten PET-Tracer \(^{68}\)Ga-Pentixafor im Vergleich zur \(^{18}\)F-FDG-PET/CT
T1 - Imaging inflammation in atherosclerosis with the CXCR4-targeted PET tracer \(^{68}\)Ga-Pentixafor compared to \(^{18}\)F-FDG-PET/CT
N2 - Herz-Kreislauf-Erkrankungen zählen zu den häufigsten Todesursachen weltweit. Ein ihr zugrundeliegender pathologischer Prozess ist die Atherosklerose. Die Ruptur eines atheroskelrotischen Plaques kann lebensbedrohlich sein. Derzeit existieren weder ein evaluierter Biomarker noch eine Bildgebungstechnik, die das Risiko einer solchen Plaqueruptur und eines nachfolgenden akuten kardiovaskulären Ereignisses vorhersagen können. Um die bildgebenden Verfahren zur Detektion der Atherosklerose zu optimieren, wurde in dieser Dissertationsarbeit untersucht, ob der PET/CT-Tracer 68Ga-Pentixafor im Vergleich zu 18F-FDG bessere Ergebnisse in der Diagnostik der Atherosklerose erzielen kann.
Insgesamt wurden 144 onkologische Patienten in die Studie einbezogen, bei denen die 18F-FDG-PET/CT sowie 68Ga-Pentifaxor-PET/CT aus klinischen Gründen indiziert waren. Befunde, bei denen eine gegenüber dem Hintergrund vermehrte Speicherung ohne physiologische Erklärung nachgewiesen werden konnte, wurden als positiv bewertet. Um Unterschiede zwischen den Patienten außer Acht lassen zu können, wurde die target-to-background-ratio (TBR) berechnet. Zur Beschreibung der Speicherintensität einer Läsion wurde der standardized uptake value (SUV) bestimmt.
Nach Auswertung der Daten zeigte sich eine mäßige Korrelation der Anzahl von 68Ga-Pentixafor-positiven Läsionen mit der Anzahl der 18F-FDG positiven Läsionen. Die CXCR4-gerichtete Bildgebung mit 68Ga-Pentixafor identifizierte mehr Läsionen als die 18F-FDG-PET/CT. Bezüglich ihres Verteilungsmusters wiesen die beiden Tracer eine geringe Korrelation auf. Die Aufnahmeintensität beider Tracer korrelierte umgekehrt mit dem Ausmaß der Verkalkung. Stark verkalkte Plaques zeigten die niedrigste Traceraufnahme für beide PET-Tracer.
Weitere Studien zur Aufklärung der zugrunde liegenden biologischen Mechanismen und Quellen der CXCR4-Positivität sind in hohem Maße gerechtfertigt.
N2 - Cardiovascular diseases are among the most common causes of death worldwide. A pathological process underlying these diseases is atherosclerosis. The rupture of an atherosclerotic plaque can be life-threatening. Currently, there is neither an evaluated biomarker nor an imaging technique that can predict the risk of such a plaque rupture and subsequent acute cardiovascular event. To optimize imaging methods for the detection of atherosclerosis, this dissertation investigated whether the PET/CT tracer 68Ga-Pentixafor can achieve better diagnostic results for atherosclerosis compared to
18F-FDG. A total of 144 oncological patients were included in the study, for whom 18F-FDG-PET/CT and 68Ga-Pentixafor-PET/CT were clinically indicated. Lesions showing increased uptake compared to the background without physiological explanation were rated as positive. To disregard differences between patients, the target-to-background ratio (TBR) was calculated. To describe the uptake intensity of a lesion, the standardized uptake value (SUV) was determined. After evaluating the data, a moderate correlation was observed between the number of 68Ga-Pentixafor-positive lesions and the number of 18F-FDG-positive lesions. CXCR4-targeted imaging with 68Ga-Pentixafor identified more lesions than 18F-FDG-PET/CT. Regarding their distribution patterns, the two tracers showed a low correlation. The uptake intensity of both tracers inversely correlated with the extent of calcification. Highly calcified plaques exhibited the lowest tracer uptake for both PET tracers. Further studies to elucidate the underlying biological mechanisms and sources of CXCR4 positivity are highly warranted.
KW - Arteriosklerose
KW - Positronen-Emissions-Tomografie
KW - Chemokinrezpetor
KW - CXCR4
KW - \(^{68}\)Ga-Pentixafor
KW - \(^{18}\)F-FDG
Y1 - 2024
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-360013
ER -
TY - THES
A1 - Hildebrandt, Lysann
T1 - Das Verhältnis von Muskel- und Knochenmasse bei Kindern und jungen Erwachsenen mit Anorexia nervosa, Hypophosphatasie, Kraniopharyngeom und rheumatischen Erkrankungen
T1 - The relation of muscle mass and osseous mass with children and young adult with anorexia nervosa, hypophosphatasia, craniopharyngeoma and rheumatism illnesses
N2 - Ziel der Studie lag in der Analyse des Zusammenhangs von Muskel- und Knochenmasse als Surrogat für Kraft und Knochenfestigkeit. In der vorliegenden Arbeit wurden 265 gesunde und chronisch kranke Kinder und Jugendliche auf ihre Körperzusammensetzung untersucht.(Anorexia nervosa: 40, Hypophosphatasie: 10, Kraniopharyngeom: 12 und juveniles Rheuma: 68, Referenzgruppe: 79 gesunde weissrussische Mädchen und 56 Jungen). Die Untersuchungsergebnisse der DXA Messungen bestätigen , dass die Knochenmasse als Surrogat für Festigkeit eng mit der Muskelmasse korreliert. Mit zunehmender Muskelmasse steigt auch der BMC an. Die Ergebnisse der Studie stehen im Einklang mit dem von Frost postuliertem Regelkreis, der einen kausalen Zusammenhang zwischen Muskelkraft und Knochenfestigkeit beschrieb. Generell zeigte sich, dass das Surrogat Knochendichte diesen Zusammenhang weniger scharf beschreibt als die Knochenmasse. Darüber hinaus fanden sich Störungen des Regelkreises, deren Ursachen zum Teil Gegenstand der Abklärung in weiterführenden Studien bleiben.
N2 - The aim of the study lay in the analysis of the connection of muscle mass and osseous mass as a surrogate for strength and osseous firmness. In the present work 265 became recovers and chronically ill children and youngsters on her body composition examined. (anorexia nervosa: 40, hypophosphatasia: 10, craniopharyngeoma: 12 and juvenile rheumatisms: 68, authoritative group: 79 healthy Belorussian girls and 56 boys). The investigation results of the measurements DXA confirm that the osseous mass correlates as a surrogate for firmness closely with the muscle mass. With increasing muscle mass also rises of the BMC. The results of the study stand in the harmony with the control circuit postulated by „Frost“ which described a causal connection between muscular strength and osseous firmness.In general appeared that the surrogate describes osseous density this connection less sharply than the osseous mass. In addition, disturbances of the control circuit whose causes remain partly an object of the clarification in continuing studies were found.
KW - Knochenstoffwechsel
KW - Knochen
KW - Knochenartefakt
KW - Muskelstoffwechsel
KW - Appetitlosigkeit
KW - Rheumatismus
KW - Deutsche Rheuma-Liga
KW - Osteologie
KW - Kraniopharyngiom
KW - Cortison
KW - Rheumatismus
KW - Deutsche Rheuma-Liga
KW - Osteologie
KW - Kraniopharyngiom
KW - Cortison
KW - Rheumatism
KW - German rheumatic league
KW - Osteologie
KW - Craniopharyngioma
KW - Cortison
Y1 - 2008
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30414
ER -
TY - THES
A1 - Wäschle, Katharina
T1 - Der Einfluss heterophiler Antikörper auf die Thyreoglobulinbestimmung bei Patienten mit differenziertem Schilddrüsenkarzinom
T1 - The impact of heterophile antibodies on the measurement of serum thyroglobulin in differentiated thyroid carcinoma patients
N2 - In der vorliegenden Studie wurde der mögliche Einfluß von heterophilen Antikörpern auf die Thyreoglobulinbestimmung in der Nachsorge beim Patienten mit differenziertem Schilddrüsenkarzinom untersucht. Dazu wurde bei 201 Patientenseren der Thyreoglobulinwert auf herkömmliche Weise und in einer Parallelbestimmung nach Vorbehandlung mit heterophilen Antikörper blocking tubes bestimmt. Dieses Vorgehen ermöglichte es, einen direkten Vergleich beider Messergebnisse anzustellen und einen möglichen Einfluß heterophiler Antikörper aufzudecken. Darüber hinaus wurde das selbe Verfahren bei einer heterogenen Kontrollgruppe angewandt. In 99% der Proben ergab sich kein signifikanter Unterschied zwischen den beiden Messergebnissen. Somit ist ein Einfluß von heterophilen Antikörpern auf die Thyreoglobulinbestimmung bei Patienten mit differenziertem Schilddrüsenkarzinom unwahrscheinlich.
N2 - The aim of the study was to determine the impact of heterophile antibodies on the measurement of serum thyroglobulin, thyroglobulin recovery, and thyroglobulin antibody levels in differentiated thyroid carcinoma patients. We studied serum samples of 201 individual patients that were followed in our hospital for differentiated thyroid carcinoma and 52 control samples. Samples were split; half were treates by incubating the sample for 1 h in HAB-blocking tubes, the remainder was left untreated. Subsequently thyroglobulin and thyroglobulin antibodies levels were measured in both the blockes and untreated samples. As result heterophile antibody interference is not a factor to be reckoned with in the daily practice of Tg measurement in the treatment and follow-up of differentiated thyroid carcinoma patients.
KW - Thyreoglobulin
KW - Antikörper
KW - Heterophile Antikörper
KW - Differenziertes Schilddrüsenkarzinom
KW - Thyreoglobulinbestimmung
KW - thyroglobulin
KW - heterophile antibodies
KW - measurement of serum thyroglobulin
Y1 - 2010
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-54609
ER -
TY - JOUR
A1 - Brumberg, Joachim
A1 - Kuzkina, Anastasia
A1 - Lapa, Constantin
A1 - Mammadova, Sona
A1 - Buck, Andreas
A1 - Volkmann, Jens
A1 - Sommer, Claudia
A1 - Isaias, Ioannis U.
A1 - Doppler, Kathrin
T1 - Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy
JF - Neurobiology of Disease
N2 - Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.
KW - peripheral nervous system
KW - Parkinson's disease
KW - skin biopsy
KW - MIBG scintigraphy
KW - multiple system atrophy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260061
VL - 153
ER -
TY - JOUR
A1 - Brumberg, Joachim
A1 - Beckl, Melanie
A1 - Dierks, Alexander
A1 - Schirbel, Andreas
A1 - Krebs, Markus
A1 - Buck, Andreas
A1 - Kübler, Hubert
A1 - Lapa, Constantin
A1 - Seitz, Anna Katharina
T1 - Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy
JF - Biomedicines
N2 - Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7% vs. 72.6%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.
KW - 68Ga-PSMA ligand PET/CT
KW - androgen deprivation therapy
KW - detection rate
KW - recurrent prostate cancer
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219301
SN - 2227-9059
VL - 8
IS - 11
ER -
TY - THES
A1 - Heider, Melanie
T1 - Detektionsrate der \(^{68}\)Ga-PSMA-PET/CT bei Patienten mit Rezidiv eines Prostatakarzinoms und Androgendeprivationstherapie
T1 - Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy
N2 - Die Detektion des Prostataspezifischen Membranantigens (PSMA) mittels kombinierter Positronenemissions- und Computertomographie (PET/CT) ist ein etabliertes diagnostisches Verfahren bei Patienten mit Prostatakarzinom. Hierbei ist bislang unklar, ob und wie eine bereits eingeleitete Androgendeprivationstherapie (ADT) die diagnostische Genauigkeit der PSMA-PET/CT beeinflusst. Ziel dieser Arbeit war es, die Detektionsrate der PSMA-PET/CT mit 68Ga-PSMA I&T unter ADT in Abhängigkeit des PSA-Wertes zu evaluieren und mit einer Kontrollgruppe ohne ADT zu vergleichen. In dieser retrospektiven Studie wurden Daten von Patienten mit biochemischem Rezidiv nach radikaler Prostatektomie analysiert, welche zwischen 2014 und 2018 eine PSMA-PET/CT am Universitätsklinikum Würzburg erhalten haben. Mittels Propensity Score Matching wurde für die Patienten mit ADT innerhalb der letzten 6 Monate vor Durchführung der PSMA-PET/CT eine Kontrollgruppe ohne ADT erstellt. Die Patienten mit ADT (n=62) wiesen eine signifikant höhere Detektionsrate auf als die Patienten ohne ADT (n=62). Die Traceranreicherung unterschied sich nicht signifikant in beiden Gruppen. Dagegen wiesen die Patienten mit ADT jedoch eine signifikant höhere Tumorlast auf und hatten häufiger Knochen- und Organmetastasen, sodass als Ursache für die höhere Detektionsrate der PSMA-PET/CT bei Patienten mit ADT ein fortgeschritteneres Tumorstadium angenommen wurde. Die Detektionsrate war bei den Patienten mit ADT auch bei niedrigen PSA-Werten hoch. Es scheint daher nicht erforderlich zu sein, eine bestehende ADT vor Durchführung der PSMA-PET/CT im biochemischen Rezidiv abzusetzen und damit das Risiko einer Krankheitsprogression einzugehen. Die Korrelation des PSA-Wertes mit der Tumorlast in der PSMA-PET/CT war bei Patienten mit ADT geringer ausgeprägt als bei Patienten ohne ADT. Patienten unter ADT könnten daher von einer regelmäßigen Durchführung der PSMA-PET/CT zur Überwachung der Krankheitsprogression profitieren. Hier bleibt allerdings eine Kosten-Nutzen-Analyse abzuwarten, da dies deutlich aufwendiger und teurer ist als die Bestimmung des PSA-Wertes.
N2 - Detection of prostate specific membrane antigen (PSMA) by combined positron emission tomography and computed tomography (PET/CT) is an established diagnostic procedure in patients with prostate cancer. So far it is unclear whether an already initiated androgen deprivation therapy (ADT) influences the diagnostic accuracy of PSMA-PET/CT. The aim of this study was to evaluate the effect of ADT on the detection rate of PSMA-PET/CT with 68Ga-PSMA I&T. In this retrospective study, data from patients with biochemical recurrence after radical prostatectomy who received PSMA-PET/CT at the University Hospital of Würzburg between 2014 and 2018 were analyzed. Propensity score matching was used to create two balanced groups of 62 patients who either did or did not receive ADT within six months before imaging. The detection rate of PSMA-PET/CT was significantly higher in the group of patients with ADT than in the control group without ADT. Tracer accumulation was not significantly different in both groups. In contrast, patients with ADT had significantly higher tumor burden and more frequent bone and organ metastases, suggesting a more advanced disease stage as the reason for the higher detection rate of PSMA-PET/CT in patients with ADT. The detection rate was high in patients with ADT even at low PSA levels. Therefore, the withdrawal of ADT before PSMA-PET/CT in biochemical recurrence, thereby risking disease progression, cannot be recommended. The correlation of PSA level with tumor burden in PSMA-PET/CT is lower in patients with ADT than in patients without ADT. Patients with ADT may therefore benefit from routine performance of PSMA-PET/CT to monitor disease progression. However, a cost-benefit analysis remains to be performed, as this is significantly more time-consuming and expensive than the measuring of the PSA value.
KW - Positronen-Emissions-Tomografie
KW - Detektion
KW - Computertomografie
KW - Prostatakrebs
KW - Rezidiv
KW - Androgendeprivation
KW - Prostataspezifisches Membranantigen
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-306123
ER -
TY - JOUR
A1 - Schadt, Fabian
A1 - Israel, Ina
A1 - Samnick, Samuel
T1 - Development and Validation of a Semi-Automated, Preclinical, MRI-Template Based PET Image Data Analysis Tool for Rodents
JF - Frontiers in Neuroinformatics
N2 - AimIn PET imaging, the different types of radiotracers and accumulations, as well as the diversity of disease patterns, make the analysis of molecular imaging data acquired in vivo challenging. Here, we evaluate and validate a semi-automated MRI template-based data analysis tool that allows preclinical PET images to be aligned to a self-created PET template. Based on the user-defined volume-of-interest (VOI), image data can then be evaluated using three different semi-quantitative parameters: normalized activity, standardized uptake value, and uptake ratio.
Materials and MethodsThe nuclear medicine Data Processing Analysis tool (NU_DPA) was implemented in Matlab. Testing and validation of the tool was performed using two types of radiotracers in different kinds of stroke-related brain diseases in rat models. The radiotracers used are 2-[\(^{18}\)F]fluoro-2-deoxyglucose ([\(^{18}\)F]FDG), a metabol\(^{68}\)Ga]Ga-Fucoidan, a target-selective radioligand specifically binding to p-selectin. After manual image import, the NU_DPA tool automatically creates an averaged PET template out of the acquired PET images, to which all PET images are then aligned onto. The added MRI template-based information, resized to the lower PET resolution, defines the VOI and also allows a precise subdivision of the VOI into individual sub-regions. The aligned PET images can then be evaluated semi-quantitatively for all regions defined in the MRI atlas. In addition, a statistical analysis and evaluation of the semi-quantitative parameters can then be performed in the NU_DPA tool.
ResultsUsing ischemic stroke data in Wistar rats as an example, the statistical analysis of the tool should be demonstrated. In this [\(^{18}\)F]FDG-PET experiment, three different experimental states were compared: healthy control state, ischemic stroke without electrical stimulation, ischemic stroke with electrical stimulation. Thereby, statistical data evaluation using the NU_DPA tool showed that the glucose metabolism in a photothrombotic lesion can be influenced by electrical stimulation.
ConclusionOur NU_DPA tool allows a very flexible data evaluation of small animal PET data in vivo including statistical data evaluation. Using the radiotracers [\(^{18}\)F]FDG and [\(^{68}\)Ga]Ga-Fucoidan, it was shown that the semi-automatic MRI-template based data analysis of the NU_DPA tool is potentially suitable for both metabolic radiotracers as well as target-selective radiotracers.
KW - data analysis
KW - Matlab
KW - MRI
KW - PET
KW - positron emission tomography
KW - preclinical imaging
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240289
SN - 1662-5196
VL - 15
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Lapa, Constantin
A1 - Serfling, Sebastian E.
A1 - Buck, Andreas K.
A1 - Seitz, Anna Katharina
A1 - Meyer, Philipp T.
A1 - Ruf, Juri
A1 - Michalski, Kerstin
T1 - Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [\(^{177}\)Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome
JF - Cancers
N2 - Simple Summary
Discordant FDG-positive but PSMA-negative (FDG+/PSMA−) metastases constitute a negative prognostic marker of overall survival in patients undergoing PSMA radioligand therapy (RLT). The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions, which occur during or after PSMA RLT. In a retrospective bicentric analysis of 32 patients undergoing PSMA RLT and follow-up dual tracer staging with PSMA and FDG PET/CT, FDG+/PSMA− lesions occurred in a limited number of patients. However, the presence of FDG+/PSMA− lesions appears not to have a significant impact on the OS, but further studies are needed to establish the clinical relevance of such lesions.
Abstract
Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [\(^{18}\)F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.
KW - PSMA
KW - FDG
KW - PET/CT
KW - prostate cancer
KW - radioligand therapy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245168
SN - 2072-6694
VL - 13
IS - 17
ER -
TY - CHAP
A1 - Werner, Rudolf A.
A1 - Marcus, Charles
A1 - Sheikhbahaei, Sara
A1 - Higuchi, Takahiro
A1 - Solnes, Lilja B.
A1 - Rowe, Steven P.
A1 - Buck, Andreas K.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
T1 - Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method
T2 - Journal of Nuclear Medicine
N2 - No abstract available.
KW - Parkinson-Krankheit
KW - SPECT
KW - Parkinson
KW - Parkinson Disease
KW - DaTscan
KW - Ioflupane
KW - molecular imaging
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162208
UR - http://jnm.snmjournals.org/content/59/supplement_1/626.abstract
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI.
VL - 59
IS - Supplement No. 1
SP - 626
ER -
TY - JOUR
A1 - Herrmann, Ken
A1 - Queiroz, Marcelo
A1 - Huellner, Martin W.
A1 - Barbosa, Felipe de Galiza
A1 - Buck, Andreas
A1 - Schaefer, Niklaus
A1 - Stolzman, Paul
A1 - Veit-Haibach, Patrick
T1 - Diagnostic performance of FDG-PET/MRI and WB-DW-MRI in the evaluation of lymphoma: a prospective comparison to standard FDG-PET/CT
JF - BMC Cancer
N2 - Background: Use of FDG-PET/CT for staging and restaging of lymphoma patients is widely incorporated into current practice guidelines. Our aim was to prospectively evaluate the diagnostic performance of FDG-PET/MRI and WB-DW-MRI compared with FDG-FDG-PET/CT using a tri-modality PET/CT-MRI system.
Methods: From 04/12 to 01/14, a total of 82 FDG-PET/CT examinations including an additional scientific MRI on a tri-modality setup were performed in 61 patients. FDG-PET/CT, FDG-PET/MRI, and WB-DW-MRI were independently analyzed. A lesion with a mean ADC below a threshold of 1.2 x 10\(^{-3}\) mm\(^2\)/s was defined as positive for restricted diffusion. FDG-PET/CT and FDG-PET/MRI were evaluated for the detection of lesions corresponding to lymphoma manifestations according to the German Hodgkin Study Group. Imaging findings were validated by biopsy (n = 21), by follow-up imaging comprising CT, FDG-PET/CT, and/or FDG-PET/MRI (n = 32), or clinically (n = 25) (mean follow-up: 9.1 months).
Results: FDG-PET/MRI and FDG-PET/CT accurately detected 188 lesions in 27 patients. Another 54 examinations in 35 patients were negative. WB-DW-MRI detected 524 lesions, of which 125 (66.5 % of the aforementioned 188 lesions) were true positive. Among the 188 lesions positive for lymphoma, FDG-PET/MRI detected all 170 instances of nodal disease and also all 18 extranodal lymphoma manifestations; by comparison, WB-DW-MRI characterized 115 (67.6 %) and 10 (55.6 %) lesions as positive for nodal and extranodal disease, respectively. FDG-PET/MRI was superior to WB-DW-MRI in detecting lymphoma manifestations in patients included for staging (113 vs. 73), for restaging (75 vs. 52), for evaluation of high-(127 vs. 81) and low-grade lymphomas (61 vs. 46), and for definition of Ann Arbor stage (WB-DW-MRI resulted in upstaging in 60 cases, including 45 patients free of disease, and downstaging in 4).
Conclusion: Our results indicate that FDG-PET/CT and FDG-PET/MRI probably have a similar performance in the clinical work-up of lymphomas. The performance of WB-DW-MRI was generally inferior to that of both FDG-PET-based methods but the technique might be used in specific scenarios, e.g., in low-grade lymphomas and during surveillance.
KW - response evaluation
KW - FDG-PET/MRI
KW - FDG-PET/CT
KW - FDG
KW - WB-DW-MRI
KW - whole-body
KW - involvement
KW - coefficient
KW - lymphoma
KW - B-cell lymphoma
KW - diffusion weighted MRI
KW - whole body MRI
KW - Hodgkin-lymphoma
KW - 1st International Workshop
KW - malignant lymphoma
KW - initial experience
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136039
VL - 15
IS - 1002
ER -
TY - THES
A1 - Thies, Elena-Daphne Dorothée
T1 - Die Prognose des differenzierten Schilddrüsenkarzinoms in Abhängigkeit von der zum Erreichen eines erkrankungsfreien Zustands benötigten Zahl der I-131-Therapien
T1 - The number of 131-I therapy courses needed to archieve complete remission is an indicator of prognosis in patients with differentiated thyroid carcinoma
N2 - Ziel:
Abschätzung der Risiken des Rezidivs des differenzierten Schilddrüsenkarzinoms, der Karzinom-bedingten Mortalität und der Karzinom-bedingten Reduktion der Lebenserwartung in Abhängigkeit von der Anzahl der zum Erreichen eines krankheitsfreien Zustands benötigten I-131-Therapien (Radioiodtherapien) und der für die Krankheitsfreiheit benötigten kumulativen Aktivität.
Methoden:
Analyse anhand von in der Würzburger Schilddrüsenkarzinom-Datenbank erfassten Verlaufsdaten unter Berücksichtigung eigener zusätzlicher Erhebungen zum follow-up.von 896 Patienten, die nach einer oder mehreren Radioiodtherapien im Therapieverlauf Erkrankungsfreiheit erreichten (negative TSH-stimulierte Thyreoglobulin-Messung in Kombination mit einer negativen I-131-Ganzkörperszintigraphie).
Ergebnisse:
Die erfassbare Nachsorgedauer betrug in Median 9.0 Jahre (Spannbreite 0.1-31.8 Jahre). Rezidiv-Raten nach 5 und 10 Jahren und am Ende der Nachsorge betrugen 1,0±0,3%, 4,0±0,7% und 6,2±1,1%. Die Schilddrüsenkarzinom-bedingte Sterberate betrug jeweils 0,1±0,1%, 0,5±0,3% und 3,4±1,1%.
Mit einer zunehmenden Anzahl von benötigten Radioiodtherapien nahm die Rezidivrate zu (p=0.001). Die Schilddrüsenkarzinom-bedingte Sterblichkeitsrate ist ab 4 benötigten Radioiodtherapien erhöht. Bei Patienten, die nach einer Radioiodtherapie krankheitsfrei waren, finden sich zwischen Niedrig- und Hochrisikopatienten keine Unterschiede bezüglich Rezidiv- und Sterblichkeitsrate. Bei Patienten, die zwei Radioiodtherapien benötigten, waren Rezidiv- und Sterblichkeitsrate der Hochrisikopatienten erhöht.
Bezüglich der kumulativ benötigten Aktivität zeigten sich nur bei Patienten, die eine kumulative Aktivität von über 22,2 GBq benötigten, erhöhte Rezidiv- und Sterberaten.
Im vorliegenden Studienkollektiv mit einer inhärent guten Prognose zeigte sich eine uneingeschränkte Lebenserwartung unabhängig von der benötigen Anzahl der Radioiodtherapien oder der benötigten kumulativen Aktivität.
Fazit:
Falls mehr als eine Radioiodtherapie oder eine hohe kumulative I-131 Aktivität benötigt wird, um einen krankheitsfreien Zustand zu erreichen, muss mit einer Rezidiv- und Schilddrüsenkarzinom-bedingten Sterblichkeits-Rate gerechnet werden, vor allem bei Hochrisikopatienten.
N2 - Purpose:
To assess the risk of differentiated thyroid cancer (DTC) recurrence, DTC-related mortality and life expectancy in relation to the number of courses of 131-I therapy (RIT) and cumulative 131-I activities required to achieve complete remission (CR).
Methods:
The study was a database review of 1,229 patients with DTC, 333 without and 896 with CR (negative TSHstimulated thyroglobulin and negative 131-I diagnostic wholebody scintigraphy) after one or more courses of RIT.
Results:
The median follow-up was 9.0 years (range 0.1–31.8 years) after CR. Recurrence rates at 5 years, 10 years and the end of follow-up were 1.0±0.3 %, 4.0±0.7 % and 6.2 ±1.1 %, and DTC-related mortality was 0.1±0.1 %, 0.5± 0.3 % and 3.4±1.1 %, respectively.
Recurrence rates also increased with an increasing number of RIT courses required (p=0.001). DTC-related mortality increased from four RIT courses.
In patients with CR after one RIT course, there were no differences in recurrence or DTC-related mortality rates between low-risk and high-risk patients. In patients requiring two RIT courses these rates remain elevated in high-risk patients. Recurrence and DTC-related mortality rates were only significantly elevated in those requiring a cumulative activity over 22.2 GBq (600 mCi) from multiple RIT courses for CR.
Regardless of the number of RIT courses or activity needed, life expectancy was not significantly lowered.
Conclusion:
If more than one RIT course is needed to achieve CR, higher recurrence and DTC-related mortality rates are observed, especially in high-risk patients. Patients requiring >22.2 GBq 131-I for CR should be followed in the same way as patients in whom CR is never reached as long-term mortality rates are similar.
KW - Differentiated thyroid carcinoma
KW - Schilddrüsenkarzinom
KW - 131-I Ablation
KW - Prognose
KW - Überleben
KW - Differentiated thyroid carcinoma
KW - 131-I ablation
KW - prognosis
KW - life expectancy
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110981
N1 - Die Doktorarbeit wurde unter dem englischen Titel: "The number of 131-I therapy courses needed to archieve complete remission is an indicator of prognosis in patients with differentiated thyroid carcinoma.", publiziert. Dies entspricht nicht hundertprozentig der deutschen Übersetzung und enthält schon Ergebnisse.
ER -
TY - JOUR
A1 - Brumberg, Joachim
A1 - Schröter, Nils
A1 - Blazhenets, Ganna
A1 - Frings, Lars
A1 - Volkmann, Jens
A1 - Lapa, Constantin
A1 - Jost, Wolfgang H.
A1 - Isaias, Ioannis U.
A1 - Meyer, Philipp T.
T1 - Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy
JF - NPJ Parkinsons Disease
N2 - [\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.
KW - clinical diagnosis
KW - F-18-FDG PET
KW - disease
KW - dementia
KW - accuracy
KW - stimulation
KW - guidelines
KW - criteria
KW - brain
KW - risk
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230675
VL - 6
ER -
TY - JOUR
A1 - Wester, Hans Jürgen
A1 - Keller, Ulrich
A1 - Schottelius, Margret
A1 - Beer, Ambros
A1 - Philipp-Abbrederis, Kathrin
A1 - Hoffmann, Frauke
A1 - Šimeček, Jakub
A1 - Gerngross, Carlos
A1 - Lassmann, Michael
A1 - Herrmann, Ken
A1 - Pellegata, Natalia
A1 - Rudelius, Martina
A1 - Kessler, Horst
A1 - Schwaiger, Markus
T1 - Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging
JF - Theranostics
N2 - Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [\(^{68}\)Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [\(^{68}\)Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [\(^{68}\)Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [\(^{68}\)Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders.
KW - acute myeloid leukemia
KW - prognostic value
KW - therapeutic target
KW - chemokine receptor
KW - CXCR4
KW - lymphoma
KW - in vivo imaging
KW - positron emission tomography
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144537
VL - 5
IS - 6
ER -
TY - JOUR
A1 - Schumann, S.
A1 - Scherthan, H.
A1 - Pfestroff, K.
A1 - Schoof, S.
A1 - Pfestroff, A.
A1 - Hartrampf, P.
A1 - Hasenauer, N.
A1 - Buck, A. K.
A1 - Luster, M.
A1 - Port, M.
A1 - Lassmann, M.
A1 - Eberlein, U.
T1 - DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with \(^{131}\)I
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Aim
The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [\(^{131}\)I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy.
Material and methods
Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [\(^{131}\)I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70% ethanol and stored at − 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs).
Results
Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h\(^{−1}\), which is in good agreement with data obtained from external irradiation with γ- or X-rays.
Conclusion
This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after \(^{131}\)I exposure is comparable to that of external irradiation with γ- or X-rays.
KW - DNA Damage Repair
KW - Radioiodine Therapy
KW - γ-h2ax
KW - 53BP1
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258863
UR - https://link.springer.com/article/10.1007/s00259-021-05605-8
ER -
TY - JOUR
A1 - Schumann, Sarah
A1 - Scherthan, Harry
A1 - Frank, Torsten
A1 - Lapa, Constantin
A1 - Müller, Jessica
A1 - Seifert, Simone
A1 - Lassmann, Michael
A1 - Eberlein, Uta
T1 - DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [\(^{68}\)Ga]Ga-PSMA I&T
JF - Cancers
N2 - The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.
KW - DNA double-strand breaks
KW - γ-H2AX
KW - 53BP1
KW - nuclear medicine
KW - dosimetry
KW - Ga-68
KW - PSMA
KW - PET/CT
KW - contrast agent
KW - prostate cancer
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200585
SN - 2072-6694
VL - 12
IS - 2
ER -
TY - JOUR
A1 - Schumann, Sarah
A1 - Eberlein, Uta
A1 - Muhtadi, Razan
A1 - Lassmann, Michael
A1 - Scherthan, Harry
T1 - DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223
JF - Scientific Reports
N2 - Irradiation with high linear energy transfer α-emitters, like the clinically used Ra-223 dichloride, severely damages cells and induces complex DNA damage including closely spaced double-strand breaks (DSBs). As the hematopoietic system is an organ-at-risk for the treatment, knowledge about Ra-223-induced DNA damage in blood leukocytes is highly desirable. Therefore, 36 blood samples from six healthy volunteers were exposed ex-vivo (in solution) to different concentrations of Ra-223. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the decay, ranging from 0 to 142 mGy. γ-H2AX + 53BP1 co-staining and analysis was performed in leukocytes isolated from the irradiated blood samples. For DNA damage quantification, leukocyte samples were screened for occurrence of α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values, being in agreement with a negligible β-contribution (3.7%) to the total absorbed dose to the blood. Our calibration curve will contribute to the biodosimetry of Ra-223-treated patients and early after incorporation of α-emitters.
KW - alpha particles
KW - blood
KW - DNA Breaks
KW - double-stranded
KW - gamma rays
KW - healthy volunteers
KW - humans
KW - leukocytes
KW - radiation effects
KW - radium
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175596
VL - 8
IS - 2286
ER -
TY - JOUR
A1 - Tamihardja, Jörg
A1 - Zehner, Leonie
A1 - Hartrampf, Philipp E.
A1 - Cirsi, Sinan
A1 - Wegener, Sonja
A1 - Buck, Andreas K.
A1 - Flentje, Michael
A1 - Polat, Bülent
T1 - Dose-escalated salvage radiotherapy for macroscopic local recurrence of prostate cancer in the prostate-specific membrane antigen positron emission tomography era
JF - Cancers
N2 - Simple Summary
Prostate cancer often relapses after initial radical prostatectomy, and salvage radiotherapy offers a second chance of cure for relapsed patients. Modern imaging techniques, especially prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), enable radiation oncologists to target radiotherapy at the involved sites of disease. In a group of patients, PSMA PET/CT imaging can detect a macroscopic local recurrence with or without locoregional lymph node metastasis. In these cases, an escalation of the radiotherapy dose is often considered for controlling the visible tumor mass. As the evidence for dose-escalated salvage radiotherapy for macroscopic recurrent prostate cancer after PSMA PET/CT imaging is still limited, we address this topic in the current analysis. We found that the outcome of patients with dose-escalated salvage radiotherapy for macroscopic prostate cancer recurrence is encouragingly favorable, while the toxicity is very limited.
Abstract
Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3–72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1% (95% CI: 81.1–97.8%) and the three-year metastasis-free survival rate reached 96.2% (95% CI: 91.2–100.0%). The cumulative three-year late grade 3 GU toxicity rate was 3.4%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.
KW - prostate cancer
KW - salvage radiotherapy
KW - macroscopic recurrence
KW - PSMA PET/CT
KW - simultaneous integrated boost
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290302
SN - 2072-6694
VL - 14
IS - 19
ER -
TY - THES
A1 - Soares Machado, Jéssica
T1 - Dosimetry-based Assessment of Radiation-associated Cancer risk for \(^9\)\(^9\)\(^m\)Tc-MAG3 Scans in Infants and Optimization of Administered Activities for \(^6\)\(^8\)Ga-labelled Peptides in Children and Adolescents
T1 - Dosimetrie-basierte Abschätzung des strahlungsassoziierten Krebsrisikos für \(^9\)\(^9\)\(^m\)Tc-MAG3-Scans bei Säuglingen und Optimierung der verabreichten Aktivitäten für \(^6\)\(^8\)Ga-markierte Peptide bei Kindern und Jugendlichen
N2 - In 2006, 0.18 Mio pediatric nuclear medicine diagnostic exams were performed worldwide. However, for most of the radiopharmaceuticals used data on biokinetics and, as a consequence on dosimetry, are missing or have not been made publicly available. Therefore, most of the dosimetry assessments presented today for diagnostic agents in children and adolescents rely on the biokinetics data of adults. Even for one of the most common nuclear medicine exams for this patient group, renal scintigraphy with 99mTc-MAG3 for assessing renal function measured data on biokinetics is available only from a study performed on four children of different ages. In particular, renal scans are among the most frequent exams performed on infants and toddlers. Due to the young age, this patient group can be classified as a risk group with a higher probability of developing stochastic radiation effects compared to adults. As there are only limited data on biokinetics and dosimetry in this patient group, the aim of this study is to reassess the dosimetry and the associated radiation risk for a larger number of infants undergoing 99mTc-MAG3 renal scans based on a retrospective analysis of existing patient data.
Data were collected retrospectively from 34 patients younger than 20 months with normal (20 patients) and abnormal renal function (14 patients) undergoing 99mTc-MAG3 scans. The patient-specific organ activity was estimated based on a retrospective calibration which was performed based on a set of two 3D-printed infant kidneys (newborns: 8.6 ml; 1-year-old: 23.4 ml) filled with known activities. Both phantoms were scanned at different positions along the anteroposterior axis inside a water phantom, providing depth- and size-dependent attenuation correction factors for planar imaging. Time-activity curves were determined by drawing kidney, bladder, and whole body regions-of-interest for each patient, and subsequently applying the calibration factor for conversion of counts to activity. Patient-specific time-integrated activity coefficients were obtained by integrating the organ-specific time-activity curves. Absorbed and effective dose coefficients for each patient were assessed with OLINDA/EXM for the provided newborn and 1-year-old phantom. Based on absorbed dose values, the radiation risk estimation was performed individually for each of the 34 patients with the National Cancer Institute’s Radiation Risk Assessment Tool.
The patients’ organ-specific mean absorbed dose coefficients for the patients with normal renal function were 0.04±0.03 mGy/MBq for the kidneys and 0.27±0.24 mGy/MBq for the bladder. This resulted in a mean effective dose coefficient of 0.02±0.02 mSv/MBq. Based on the dosimetry results, the evaluation of the excess lifetime risk (ELR) for the development of radiation-induced cancer showed that the group of newborns has an ELR of 16.8 per 100,000 persons, which is higher in comparison with the 1-year-old group with an ELR of 14.7 per 100,000 persons. With regard to the 14 patients with abnormal renal function, the mean values for the organ absorbed dose coefficients for the patients were: 0.40±0.34 mGy/MBq for the kidneys and 0.46±0.37 mGy/MBq for the bladder. The corresponding effective dose coefficients (mSv/MBq) was: 0.05±0.02 mSv/MBq. The mean ELR (per 100,000 persons) for developing cancer from radiation exposure for patients with abnormal renal function was 29.2±18.7 per 100,000 persons.
As a result, the radiation-associated stochastic risk increases with the organ doses, taking age- and gender-specific influences into account. Overall, the lifetime radiation risk associated with the 99mTc-MAG3 scans is very low in comparison to the general population risk for developing cancer.
Furthermore, due to the increasing demand for PET-scans in children and adolescents with 68Ga-labelled peptides, in this work published data sets for those compounds were analyzed to derive recommendations for the administered activities in children and adolescents. The recommendation for the activities to be administered were based on the weight-independent effective dose model, proposed by the EANM Pediatric Dosage Card for application in pediatric nuclear medicine. The aim was to derive recommendations on administered activities for obtaining age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card, to determine the radiopharmaceutical class of 68Ga-labeled peptides (“multiples”), and to calculate the baseline activities based on the biokinetics of these compounds and an upper limit of the administered activity of 185 MBq for an adult. Analogous to 18F-fluoride, a minimum activity of 14 MBq is recommended. As a result, for those pediatric nuclear medicine applications involving 68Ga-labeled peptides, new values for the EANM dosage card were proposed and implemented based on the results derived in this work.
Overall, despite the low additional radiation-related cancer risk, all efforts should be undertaken to optimize administered activities in children and adolescents for obtaining sufficient diagnostic information with minimal associated radiation risk.
N2 - Im Jahr 2006 wurden weltweit 0,18 Mio. nuklearmedizinische Diagnostikuntersuchungen bei Kindern durchgeführt. Für die meisten Radiopharmazeutika fehlen jedoch Daten zur Biokinetik und damit zur Dosimetrie oder diese wurden nicht öffentlich zugänglich gemacht. Daher basieren die meisten der heute vorgestellten Dosimetriedaten für Diagnostika bei Kindern und Jugendlichen auf den biokinetischen Daten von Erwachsenen. Selbst für eine der häufigsten nuklearmedizinischen Untersuchungen für diese Patientengruppe, die Nierenszintigraphie mit 99mTc-MAG3 für Bestimmung der Nierenfunktion, wurden Daten zur Biokinetik bisher nur für vier Kinder unterschiedlichen Alters erhoben. Insbesondere Nierenuntersuchungen gehören zu den häufigsten Untersuchungen bei Säuglingen und Kleinkindern. Aufgrund des jungen Alters kann diese Patientengruppe als Hochrisikogruppe mit einer höheren Wahrscheinlichkeit für das Eintreten stochastischer Strahlenwirkungen im Vergleich zu Erwachsenen eingestuft werden. Da es in dieser Patientengruppe nur begrenzte Daten zur Biokinetik und Dosimetrie gibt, ist das Ziel dieser Arbeit, die Dosimetrie und das damit verbundene Strahlenrisiko für eine größere Anzahl von Kleinkindern, die sich 99mTc-MAG3-Nierenscans unterziehen, auf der Grundlage einer retrospektiven Analyse bestehender Patientendaten neu zu bewerten.
Die Daten wurden retrospektiv von 34 Patienten unter 20 Monaten mit normaler (20 Patienten) und eingeschränkter Nierenfunktion (14 Patienten) erhoben, bei denen 99mTc-MAG3-Scans durchgeführt wurden. Die patientenspezifische Organaktivität wurde basierend auf einer retrospektiven Kalibrierung abgeschätzt. Diese Kalibrierung basiert auf einem Satz von zwei 3D-gedruckten Säuglingsnieren, die mit bekannten Aktivitäten gefüllt wurden. Beide Phantome wurden an verschiedenen Positionen entlang der anteroposterioren Achse innerhalb eines Wasserphantoms gescannt und lieferten tiefen- und größenabhängige Schwächungskorrekturfaktoren für die planare Bildgebung. Die Zeit-Aktivitäts-Kurven wurden bestimmt, indem für jeden Patienten Nieren-, Blasen- und Ganzkörperregionen eingezeichnet und anschließend der entsprechende Kalibrierfaktor für die Umwandlung der Zählraten in Aktivität angewendet wurde. Patientenspezifische zeitintegrierte Aktivitätskoeffizienten wurden durch Integration der organspezifischen Zeit-Aktivitätskurven ermittelt. Die Energie- und effektiven Dosiskoeffizienten für jeden Patienten wurden mit OLINDA/EXM für das bereitgestellte Neugeborenen- und 1-Jahres-Phantom ermittelt. Basierend auf diesen Werten für die Energiedosen wurde eine individuelle Abschätzung des Strahlenrisikos für jeden der 34 Patienten mit dem Radiation Risk Assessment Tool des National Cancer Institute durchgeführt.
Die organspezifischen mittleren Energiedosiskoeffizienten der Patienten mit normaler Nierenfunktion lagen bei 0,04±0,03 mGy/MBq für die Nieren und 0,27±0,24 mGy/MBq für die Blase, was in einem mittleren effektiven Dosiskoeffizienten von 0,02±0,02 mSv/MBq resultiert. Basierend auf den Ergebnissen der Dosimetrie, zeigte die Auswertung des zusätzlichen Lebenszeitrisikos ("excess lifetime risk", ELR) für die Entwicklung von strahleninduziertem Krebs, dass die Gruppe der Neugeborenen ein ELR von 16,8 pro 100.000 Personen aufweist, was höher ist als das der Gruppe der 1-jährigen mit 14,7 pro 100.000 Personen. Bei den 14 Patienten mit abnormaler Nierenfunktion waren die Mittelwerte für die Koeffizienten der organspezifischen Energiedosen für die Patienten: 0,40±0,34 mGy/MBq für die Nieren; 0,46±0,37 mGy/MBq für die Blase. Der effektivendosiskoeffizienten (mSv/MBq) waren: 0,05±0,02 mSv/MBq. Der mittlere ELR (pro 100.000 Personen) für die Entstehung von Krebs durch die Strahlenexposition von Patienten mit abnormaler Nierenfunktion betrug 29,2±18,7 pro 100.000 Personen.
Das mit der Strahlung verbundene stochastische Risiko steigt mit den Organdosen unter Berücksichtigung alters- und geschlechtsspezifischer Einflüsse. Im Allgemeinen ist das mit den 99mTc-MAG3-Scans verbundene lebenslange Strahlenrisiko im Vergleich zum allgemeinen Bevölkerungsrisiko für die Entstehung von Krebs sehr gering.
Aufgrund der steigenden Nachfrage nach PET-Scans bei Kindern und Jugendlichen mit 68Ga-markierten Peptiden wurden zusätzlich publizierte Datensätze für diese Verbindungen analysiert, um Empfehlungen für zu verabreichende Aktivitäten bei Kindern und Jugendlichen abzuleiten.
Die Dosisberechnungen dazu basierten auf dem Modell einer gewichtsunabhängigen effektiven Dosis, das von der EANM Pediatric Dosage Card für den Einsatz in der pädiatrischen Nuklearmedizin vorgeschlagen wurde. Ziel war es, Empfehlungen zu verabreichenden Aktivitäten so aufzuteilen, dass sich altersunabhängige effektive Dosen ergeben. Dazu wurden die entsprechenden gewichtsabhängigen effektiven Dosiskoeffizienten gemäß dem Formalismus der EANM-Dosierungsempfehlung neu berechnet, um die radiopharmazeutische Klasse der 68Ga-markierten Peptide ("Multiples") zu bestimmen und die Werte für Basisaktivität zu berechnen. Diese basierend auf den Biokinetiken dieser Verbindungen und einer Obergrenze der verabreichten Aktivität von 185 MBq für einen Erwachsenen. Analog zu 18F-Fluorid, wird eine Mindestaktivität von 14 MBq empfohlen. Darauf basierend wurden für die pädiatrischen nuklearmedizinischen Anwendungen mit 68Ga-markierten Peptiden neue Werte für die EANM-Dosierungsempfehlung vorgeschlagen.
Insgesamt sollten, trotz des geringen zusätzlichen strahlenbedingten Krebsrisikos, alle Anstrengungen unternommen werden, um die verabreichten Aktivitäten bei Kindern und Jugendlichen zu optimieren, um ausreichende diagnostische Informationen bei minimalem zusätzlichem Strahlenrisiko zu erhalten.
KW - Biokinetics
KW - Absorbed Doses
KW - Risk Assessment
KW - Pediatric Patients
KW - Dosimetry
KW - Nuclear Medicine
KW - Pediatric Nuclear Medicine
KW - Diagnostic Imaging Exams
KW - Radiation Protection
KW - Administered Activities
KW - Radiation-associated Cancer Risk
KW - Ga-68-labelled Peptides
KW - Tc-99m-MAG3 Scans
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192640
ER -
TY - JOUR
A1 - Konijnenberg, Mark
A1 - Herrmann, Ken
A1 - Kobe, Carsten
A1 - Verburg, Frederik
A1 - Hindorf, Cecilia
A1 - Hustinx, Roland
A1 - Lassmann, Michael
T1 - EANM position paper on article 56 of the Council Directive 2013/59/Euratom (basic safety standards) for nuclear medicine therapy
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - The EC Directive 2013/59/Euratom states in article 56 that exposures of target volumes in nuclear medicine treatments shall be individually planned and their delivery appropriately verified. The Directive also mentions that medical physics experts should always be appropriately involved in those treatments. Although it is obvious that, in nuclear medicine practice, every nuclear medicine physician and physicist should follow national rules and legislation, the EANM considered it necessary to provide guidance on how to interpret the Directive statements for nuclear medicine treatments.
For this purpose, the EANM proposes to distinguish three levels in compliance to the optimization principle in the directive, inspired by the indication of levels in prescribing, recording and reporting of absorbed doses after radiotherapy defined by the International Commission on Radiation Units and Measurements (ICRU):
Most nuclear medicine treatments currently applied in Europe are standardized. The minimum requirement for those treatments is ICRU level 1 (“activity-based prescription and patient-averaged dosimetry”), which is defined by administering the activity within 10% of the intended activity, typically according to the package insert or to the respective EANM guidelines, followed by verification of the therapy delivery, if applicable.
Non-standardized treatments are essentially those in developmental phase or approved radiopharmaceuticals being used off-label with significantly (> 25% more than in the label) higher activities. These treatments should comply with ICRU level 2 (“activity-based prescription and patient-specific dosimetry”), which implies recording and reporting of the absorbed dose to organs at risk and optionally the absorbed dose to treatment regions.
The EANM strongly encourages to foster research that eventually leads to treatment planning according to ICRU level 3 (“dosimetry-guided patient-specific prescription and verification”), whenever possible and relevant.
Evidence for superiority of therapy prescription on basis of patient-specific dosimetry has not been obtained. However, the authors believe that a better understanding of therapy dosimetry, i.e. how much and where the energy is delivered, and radiobiology, i.e. radiation-related processes in tissues, are keys to the long-term improvement of our treatments.
KW - nuclear medicine therapy
KW - dosimetry
KW - optimization
KW - BSS directive
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235280
SN - 1619-7070
VL - 48
ER -
TY - JOUR
A1 - Aerts, An
A1 - Eberlein, Uta
A1 - Holm, Sören
A1 - Hustinx, Roland
A1 - Konijnenberg, Mark
A1 - Strigari, Lidia
A1 - van Leeuwen, Fijs W. B.
A1 - Glatting, Gerhard
A1 - Lassmann, Michael
T1 - EANM position paper on the role of radiobiology in nuclear medicine
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.
KW - radionuclide therapy
KW - radiobiology
KW - dosimetry
KW - biodosimetry
KW - biomarkers
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265595
VL - 48
IS - 11
ER -
TY - JOUR
A1 - Kläsner, Benjamin
A1 - Buchmann, Niels
A1 - Gempt, Jens
A1 - Ringel, Florian
A1 - Lapa, Constantin
A1 - Krause, Bernd Joachim
T1 - Early [\(^{18}\)F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology
JF - PLoS One
N2 - Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [\(^{18}\)F]O-(2-[\(^{18}\)F]-fluoroethyl)-L-tyrosine ([\(^{18}\)F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [\(^{18}\)F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [\(^{18}\)F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [\(^{18}\)F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [\(^{18}\)F]FET-PET seems to be feasible.
KW - glioblastoma multiforme
KW - brain tumors
KW - C-11-methionine pet
KW - positron-emission-tomography
KW - improves
KW - survival
KW - delineation
KW - radiotherapy
KW - methionine pet
KW - cerebral gliomas
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139549
VL - 10
IS - 10
ER -
TY - JOUR
A1 - Werner, Rudolf A.
T1 - Editorial: Cardiac Innervation Imaging as a Risk Stratification Tool for Potential Device Therapy Candidates
JF - Journal of Nuclear Cardiology
N2 - As a scintigraphic approach evaluating cardiac nerve integrity, \(^{123}\)I-metaiodobenzylguanidine (123I-mIBG) has been recently Food and Drug Administration approved. A great deal of progress has been made by the prospective ADMIRE-HF trial, which primarily demonstrated the association of denervated myocardium assessed by \(^{123}\)I-mIBG and cardiac events. However, apart from risk stratification, myocardial nerve function evaluated by molecular imaging should also be expanded to other clinical contexts, in particular to guide the referring cardiologist in selecting appropriate candidates for specific therapeutic interventions. In the present issue of the Journal of Nuclear Cardiology, the use of 123I-mIBG for identifying cardiomyopathy patients, which would most likely not benefit from ICD due low risk of arrhythmias, is described. If we aim to deliver on the promise of cardiac innervation imaging as a powerful tool for risk stratification in a manner similar to nuclear oncology, studies such as the one reviewed here may imply an important step to lay the proper groundwork for a more widespread adoption in clinical practice.
KW - SPECT
KW - SPECT
KW - myocardial nerve
KW - 123I-metaiodobenzylguanidine
KW - 123I-mIBG
KW - cardiac nerve
KW - ICD
KW - arrhythmia
KW - cardiac innervation imaging
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168465
UR - https://rdcu.be/970i
SN - 1071-3581
N1 - SharedIt-Link zur Publikation:
https://rdcu.be/970i
N1 - This is a post-peer-review, pre-copyedit version of an article published in Journal of Nuclear Cardiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12350-018-01475-0
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Kobayashi, Ryohei
A1 - Wakabayashi, Hiroshi
A1 - Lapa, Constantin
A1 - Menke, Andreas
A1 - Higuchi, Takahiro
T1 - Effect of Antidepressants on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake
T2 - European Heart Journal - Cardiovascular Imaging
N2 - No abstract available.
KW - MIBG
KW - Metaiodobenzylguanidine
KW - mIBG
KW - antidepressants
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161116
SN - 2047-2404
N1 - This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of
record Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i52-53, May 2017 is available online at: 10.1093/ehjci/jex080.
VL - 18
IS - Supplement
PB - Oxford University Press
ER -
TY - JOUR
A1 - Khatri, Wajahat
A1 - Chung, Hyun Woo
A1 - Werner, Rudolf A.
A1 - Leal, Jeffrey P.
A1 - Pienta, Kenneth J.
A1 - Lodge, Martin A.
A1 - Gorin, Michael A.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
T1 - Effect of point-spread function reconstruction for indeterminate PSMA-RADS-3A lesions on PSMA-targeted PET imaging of men with prostate cancer
JF - Diagnostics
N2 - Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is emerging as an important modality for imaging patients with prostate cancer (PCa). As with any imaging modality, indeterminate findings will arise. The PSMA reporting and data system (PSMA-RADS) version 1.0 codifies indeterminate soft tissue findings with the PSMA-RADS-3A moniker. We investigated the role of point-spread function (PSF) reconstructions on categorization of PSMA-RADS-3A lesions. Methods: This was a post hoc analysis of an institutional review board approved prospective trial. Around 60 min after the administration of 333 MBq (9 mCi) of PSMA-targeted \(^{18}\)F-DCFPyL, patients underwent PET/computed tomography (CT) acquisitions from the mid-thighs to the skull vertex. The PET data were reconstructed with and without PSF. Scans were categorized according to PSMA-RADS version 1.0, and all PSMA-RADS-3A lesions on non-PSF images were re-evaluated to determine if any could be re-categorized as PSMA-RADS-4. The maximum standardized uptake values (SUVs) of the lesions, mean SUVs of blood pool, and the ratios of those values were determined. Results: A total of 171 PSMA-RADS-3A lesions were identified in 30 patients for whom both PSF reconstructions and cross-sectional imaging follow-up were available. A total of 13/171 (7.6%) were re-categorized as PSMA-RADS-4 lesions with PSF reconstructions. A total of 112/171 (65.5%) were found on follow-up to be true positive for PCa, with all 13 of the re-categorized lesions being true positive on follow-up. The lesions that were re-categorized trended towards having higher SUV\(_{max}\)-lesion and SUV\(_{max}\)-lesion/SUV\(_{mean}\)-blood-pool metrics, although these relationships were not statistically significant. Conclusions: The use of PSF reconstructions for \(^{18}\)F-DCFPyL PET can allow the appropriate re-categorization of a small number of indeterminate PSMA-RADS-3A soft tissue lesions as more definitive PSMA-RADS-4 lesions. The routine use of PSF reconstructions for PSMA-targeted PET may be of value at those sites that utilize this technology.
KW - prostate-specific membrane antigen
KW - reporting and data system
KW - positron emission tomography
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236528
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - THES
A1 - Schneider, Mara
T1 - Effects of levothyroxine on bone mineral density, muscle force and bone turnover markers: A cohort study
T1 - Langzeitwirkung von Levothyroxin auf Knochendichte, Muskelkraft und Knochenstoffwechsel: eine Kohortenstudie
N2 - The objective of this prospective observational controlled study was to evaluate potential effects and dose-response relationship of LT4 administration on BMD, parameters of bone and muscle strength, and biochemical variables of calcium homoeostasis and bone turnover.Ninety-seven men and pre-menopausal women after near total thyroidectomy and ¹³¹I remnant ablation for well-differentiated thyroid carcinoma or after strumectomy for non-toxic goitre were stratified by degree of TSH suppression and by gender in three subgroups: 28 men and 46 women on LT4 suppressive treatment and 23 women on LT4 replacement therapy. Patients were matched for age, gender and BMI to 89 healthy controls with a negative history of thyroid disease. Patients and controls were followed and studied for a mean time of 1.1±0.2 years. Peripheral volumetric total and trabecular BMD as well as bone strength (pQCT) were determined at the ultra-distal radius. Central areal BMD (DXA) was measured at the lumbar spine, left and right femoral neck as well as left and right total hip. Maximum grip strength (dynamometer) of the non-dominant forearm and serum markers of calcium and bone metabolism were assessed. BMD at the axial skeleton and muscle strength were not impaired by LT4 medication irrespective of gender, underlying diagnosis or treatment regimen. By contrast, a general trend of inversely affected total and trabecular BMD and of decreased bone strength was detected at the ultra-distal radius. Only in women on LT4 suppressive treatment, loss of total BMD at the ultra-distal radius reached a level of high significance. In women on LT4 replacement therapy, a significant decline of maximum grip strength appeared in comparison with female controls, while appendicular total and trabecular BMD as well as bone strength remained unchanged and did not differ from respective controls. In men on LT4 suppressive treatment, greater reduction of bone strength as compared to female thyroid cancer patients was marginally significant. Calcium balance was stable and serum concentrations of bone metabolism markers levelled off or rather decreased contradicting (high turnover) bone loss. The study did not reveal any dose-related differential influence of LT4 administration either on primary or secondary study endpoints in female patients. A gender-related difference of bone strength in response to LT4 suppressive treatment might not be excluded, as male thyroid cancer patients showed greater decline of bone strength despite unaffected peripheral BMD and muscle strength. In conclusion, there was only little evidence of adverse LT4 effects. For the most part, LT4 administration irrespective of degree of TSH suppression was not associated with low or accelerated loss of BMD at the peripheral and central skeleton and loss of bone and muscle strength, a finding also confirmed biochemically. The ultra-distal radius as a non-weight bearing skeletal site might be at risk for BMD reduction. According to the results, pre-menopausal women on LT4 suppressive therapy might be at risk of bone loss. The more complex approach of this study also took into account biomechanical qualities of bone material as well as structural and geometrical characteristics of bone architecture implying a causal muscle-bone interrelationship.
N2 - Diese prospektive, kontrollierte Beobachtungsstudie untersuchte den Langzeiteinfluß einer medikamentösen Behandlung mit LT4, auch unter dem Aspekt einer Dosis-Wirkungsbeziehung, auf periphere und axiale Knochendichte, periphere Knochenfestigkeit und Muskelkraft (d.h. primäre Studienendziele) sowie auf Laborparameter des Kalziums- und Knochenstoffwechsels (d.h. sekundäre Studienendziele) bei Schilddrüsenkarzinom- und Strumapatienten/-innen. Das Patientenkollektiv umfasste 97 Männer und prämenopausale Frauen unter LT4-Dauermedikation wegen Thyroidektomie und ¹³¹I Ablationstherapie bei differenziertem Schilddrüsenkarzinom oder einer Strumektomie bei euthyreoter Struma. Die Patienten wurden nach Geschlecht sowie Grad der TSH-Suppression, der abhängig von der vorliegenden Schilddrüsengrunderkrankung war, in drei Gruppen eingeteilt: 28 männliche und 46 prämenopausale Karzinompatienten/-innen unter TSH-suppressiver Therapie sowie 23 prämenopausale Strumapatientinnen unter physiologischer Schilddrüsenhormonsubstitution. 89 gesunde Freiwillige mit negativer Schilddrüsenanamnese dienten als Kontrollen, die bezüglich Alter, Geschlecht und BMI angepaßt waren. Patienten und Kontrollen wurden bei Studieneintritt und nach einem Zeitraum von 1.1±0.2 Jahren wiederholt untersucht. Bestimmt wurden die periphere volumetrische totale und trabekuläre Knochendichte sowie die periphere Knochenfestigkeit am ultra-distalen Radius (pQCT), die axiale planare Knochendichte an der Lendenwirbelsäule, am linken und rechten Schenkelhals sowie an der linken und rechten Hüfte (DXA), die maximale Griffstärke des nicht-dominanten Unterarms (Dynamometer) sowie Laborparameter des Kalziums- und Knochenstoffwechsels. Die langfristige Gabe von LT4 verringerte weder die Knochendichte am axialen Skelett noch die periphere Muskelkraft. Am ultra-distalen Radius zeigte sich eine Tendenz zu verminderter Knochenfestigkeit sowie zu verringerter totaler Knochendichte bei erhöhter trabekulärer Knochendichte. Nur bei Frauen unter TSH-suppressiver Therapie erreichte der Verlust an peripherer totaler Knochendichte ein hohes Signifikanzniveau. Frauen in Substitutionsbehandlung wiesen im Vergleich zu den weiblichen Kontrollen einen signifikanten Verlust an peripherer Muskelkraft auf bei unveränderter peripherer totaler und trabekulärer Knochendichte sowie unveränderter peripherer Knochenfestigkeit. Männer unter TSH-suppressiver Therapie zeigten tendenziell einen größeren Verlust an peripherer Knochenfestigkeit als Frauen. Die biochemischen Resultate, die einen normalen Kalziumhaushalt sowie konstante bzw. abfallende Serumkonzentrationen an Knochenstoffwechselmarkern umfassten, untermauerten die ausgebliebenen bis geringfügigen morphologischen Veränderungen am Knochen. Weder bei primären noch sekundären Studienendzielen lies sich eine Dosis-Wirkungsbeziehung nachweisen. Eine langfristige medikamentöse Behandlung mit LT4 wirkte sich nicht bzw. nur sehr geringfügig nachteilig auf die (Funktions-)Einheit von Knochen und Muskel aus. Die Gabe von LT4 war weder assoziiert mit niedrigen Ausgangswerten peripherer und axialer Knochendichte, peripherer Knochenfestigkeit und Muskelkraft noch mit einem (beschleunigten) Verlust an peripherer und axialer Knochendichte, peripherer Knochenfestigkeit und Muskelkraft. Dieses Resultat spiegelte sich auch biochemisch wider. Der ultra-distale Radius könnte einen hinsichtlich Knochendichteverlustes gefährdeten Skelettabschnitt darstellen. Für die Patientengruppe der Frauen unter TSH-suppressiver Therapie könnte sich daraus ein erhöhtes Risiko für periphere Frakturen ergeben. Diese Studie berücksichtigte auch bisher außer Acht gelassene biomechanische, strukturelle und geometrische Eigenschaften von Knochensubstanz und -architektur, denen eine eng miteinander verknüpfte, sich gegenseitig stark beeinflussende Funktionseinheit von Knochen und Muskel zugrunde liegt.
KW - Schilddrüse
KW - Muskelkraft
KW - Knochenstoffwechsel
KW - Schilddrüsenhormontherapie
KW - Knochendichte
KW - Levothyroxine
KW - bone mineral density
KW - muscle force
KW - bone metabolism
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85173
ER -
TY - THES
A1 - Wingenfeld, Bianca
T1 - Effekt der Radiosynoviorthese anhand klinischer, laborchemischer und bildgebender Parameter
T1 - Effect of radiosynoviorthesis by means of clinical, laboratory and radiological parameters
N2 - Ziel: Der Therapieerfolg der Radiosynoviorthese sollte bei rheumatoider Arthritis und anderen entzündlichen Gelenkerkrankungen anhand subjektiver, objektiver, so wie laborchemischer und bildgebender Parameter prospektiv beurteilt werden. Methode: Es wurden insgesamt 174 Gelenke bei 97 Patienten behandelt, wobei 55% der Patienten an einer rheumatoiden Arthritis und 23% an einer aktivierten Arthrose litten.Die Veränderungen 6 Monate nach einer Radiosynoviorthese wurden sowohl an subjektiven, wie auch an objektiven Parametern (Schmerz, Schwellung, Gelenk-beweglichkeit) evaluiert. Zusätzlich wurden laborchemische Parameter (CRP, BSG), bildgebende Verfahren (Skelett-szintigraphie, MRT) und Einnahme von Medikamenten beurteilt. Eine weitere Befragung zum Wiederauftreten von Beschwerden (Rezidiv) erfolgte in Zeit-räumen zwischen einem und drei Jahren nach der Radiosynoviorthese. Ergebnisse: Gute Erfolge in 60 bis 80% der Fälle zeigten sich bei der klinischen Symptomatik, sowohl auf subjektiver, als auch auf objektiver Ebene, wobei sich in der Korrelationsanalyse niedrige Werte zwischen den subjektiven und objektiven Parametern ergeben hatten. Bei 55% der Gelenke hatte sich die Schmerzintensität verringert, 23% waren gänzlich schmerzfrei. Die objektiv gemessene Änderung der Gelenkbeweglichkeit hatte bei 73% eine Besserung ergeben, 12% waren uneingeschränkt beweglich, bei 68% war die Schwellung zurückgegangen. Die Radionuklidaufnahme in der Weichteilphase der Sklettszintigraphie verminderte sich bei 58% der Gelenke, die Kernspin-tomographie ergab bei 44% der Kniegelenke einen Entzündungsrückgang. Rezidive traten nach einem bis drei Jahren nur bei 15% der Patienten auf.Die labor-chemischen Parameter sowie die Medikamenteneinnahme wurden durch die Radiosynoviorthese nicht beeinflusst. Schlussfolgerung: Die Radiosynoviorthese liefert auf subjektiver und objektiver Ebene gute Ergebnisse im Sinne einer Besserung. Sie ist dabei eine schonende Therapieform, die ohne Risiken einer Operation gleichzeitig an mehreren Gelenke vorgenommen und gegebenfalls wiederholt werden kann. Sie bietet damit somit eine gute Therapie-möglichkeit im Rahmen der interdisziplinären Behandlungsformen dar.
N2 - Aim: Effect of radiosynoviorthesis should be evaluated in a prospective study by subjective, objective, laboratory and radiological parameters in patients with rheumatoid arthritis and others inflammatory joint deseases. Methods: A total of 174 joints in 97 patients were investigated. 55% of the patients suffered from rheumatoid arthritis, 23% from active arthrosis. The effect of radiosynoviorthesis was evaluated by subjective (pain, swelling, joint-mobility) as well as by objective parameters at 6 months after radiosynoviorthesis. In addition to this medication, laboratory and radiological examinations were evaluated. Follow-up one to three years patients were asked for symptoms coming back. Results: Our results have shown a good improvement of clinical symptoms in 60-80% of cases, even though the correlations between subjective to objective parameters were low. 55% of joints had almost complete, 23% complete pain relief. 73% showed a good improvement of objective joint-mobility, 56% of joint-swelling. In 12% joint-motion was totally normal. The radiological uptake in three-bone scan was reduced in 58% of joints; in MRI a reduction of inflammation was seen in 44% of knees. Follow-up one to three years revealed symptoms coming back in only 15%. The laboratory parameters and medication did not change after radiosynoviorthesis. Conclusion: Radiosynoviorthesis showed a good improvement in subjective as well as in objective parameters.It is possible to treat more than only one joint a day and, if necessary, you can repeat the therapy without any risks of operation. Radiosynoviorthesis is a reliable method for the treatment in joint deseases among all the others.
KW - Radiosynoviorthese
KW - Rheumatoide Arthritis
KW - subj./objektive Evaluation von Schmerz
KW - Schwellung und Beweglichkeit
KW - bildgebende Parameter
KW - Radiosynoviorthesis
KW - rheumatoid arthritis
KW - subj./objective evaluation of pain
KW - swelling and joint-mobility
KW - radiological parameters
Y1 - 2001
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-1182669
ER -
TY - THES
A1 - Kaiser, Franz R.
T1 - Ein \(^{18}\)F markiertes PET-Radiopharmakon (LMI1195) zur Bildgebung des Norepinephrin-Stoffwechsels im Rattenherz
T1 - An \(^{18}\)-F labeled PET radiopharmaceutical (LMI1195) for imaging of the norepinephrine metabolism in the rat heart
N2 - Der neuartige (18)F-markierte Tracer, LMI1195 (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine) wurde für die Bildgebung des sympathischen Nervensystems entwickelt; die hohe Spezifität dieses Tracers für den neuralen Uptake-1 Mechanismus wurde bereits gezeigt in Zell-Versuchen, sowie in Studien mit Kaninchen- und nicht menschlichen Primaten zur Bestimmung des kardialen Tracer-Uptakes. Das Ziel dieser Studie war es, die Mechanismen des kardialen (18)F-LMI1195-Uptakes in der Ratte zu untersuchen, von der bekannt ist, dass es neben dem Uptake-1 Mechanismus weitere Arten der Noradrenalin-Aufnahme im Herzen gibt.
N2 - The novel PET Tracer N-[3-bromo-4-(3-18F-fluoropropoxy)-benzyl]-guanidin (LMI1195) has recently been developed for the imaging of the sympathetic nervous system. Previous studies in cell models, as well as rabbit and nonhuman primate studies have shown a high specificity for the cardiac neural uptake-1 mechanism. The aim of this study was to further assess the mechanisms of the cardiac 18-F-LMI1195 uptake in the rat heart, known to have additional, differing norepinephrine uptake mechanisms besides neural uptake-1.
KW - LMI1195
KW - Uptake-1
KW - Ratte
KW - LMI1195
KW - Uptake-1
KW - Ratte
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244335
ER -
TY - THES
A1 - Messerer, Nina
T1 - Eine neue Methode zur Erfassung von Muskelkraft und Muskelleistung der unteren Extremitäten und ihr Zusammenhang mit dem Sturzrisiko
T1 - A new technique to measure muscle force and muscle power of the lower limbs and the relation to the risk of falling
N2 - Stürze im Alter stellen ein ernstzunehmendes und häufiges Geschehen im Alter dar. Die Gründe sind multifaktoriell bedingt, wobei die Sarkopenie einen wichtigen Stellenwert einnimmt.
Eine an der Universität Würzburg entwickelte Bodenreaktionskraftmessplatte ermöglicht die Erfassung von Muskelkraft und Muskelleistung während natürlicher Bewegungsabläufe wie Kniebeugen oder Aufstehen von einem Stuhl.
In dieser Pilotstudie wurde untersucht, ob dieses Messverfahren als Screeningmethode
zur Erkennung von Muskelkraft und -leistungsdefiziten geeignet ist und ob ein Zusammenhang mit einem erhöhten Sturzvorkommen besteht. Bei 459 zu Hause lebenden mobilen Senioren zwischen dem 50. und 80. Lebensjahr wurde die Muskelkraft und Muskelleistung der unteren Extremitäten erfasst. Zudem wurden in einem Fragebogen Sturzrisikofaktoren und Stürze der letzten 12 Monate ermittelt.
Die Befunde zum Abbau von Muskelkraft und -leistung decken sich mit der gegenwärtigen Studienlage. Im Zusammenhang mit den angegegebenen Stürzen könnte anhand der Ergebnisse insbesondere die Muskelleistung eine Screeningmethode zur Einschätzung des Sturzrisikos darstellen. Weiterführende Studien scheinen anhand der Ergebnisse gerechtfertigt.
N2 - Falls in elderly are a serious and frequent event. The reasons are multi-attributed, in which the sarcopenia plays an important role.
The University Würzburg developed a ground force reaction platform which allows for measuring muscle force and muscle power during natural movements. This pilot study examines if this technique is a practicable screening method for deficits in muscle force and muscle power, as well as their relation with an increased occurrence of falls. We measured the muscle force and muscle power in 459 mobile community dwelling elderly between the age of 50 to 80 performing knee bends and chair-rise. We recorded risk factors of falling and also falls in the past 12 months using a questionnaire.
The results concerning the loss of muscle force and muscle power in age coincide with the current data. Regarding the reported falls, in particular muscle power could be a suitable method for calculating the risk of falls. In closing, further studies seem to be justified.
KW - Muskelleistung
KW - Kraftmessplatte
KW - ground force reaction platform
KW - Muskelkraft
KW - Sarkopenie
KW - Kraftmessung
KW - Sturz
KW - muscle force
KW - muscle power
KW - falls
KW - sarcopenia
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85268
ER -
TY - THES
A1 - Messerschmidt, Konstantin Felix
T1 - Einfluss der PSMA-Expression auf die Docetaxel-Sensitivität sowie systemischer Medikamente auf die Expression von PSMA, CXCR4 und SSTR2
T1 - Influence of PSMA expression on docetaxel sensitivity and of systemic drugs on PSMA, CXCR4 and SSTR2 expression
N2 - Für das klinische Management des Prostatakarzinoms werden nuklearmedizinische Verfahren zunehmend relevant. Bildgebung und Therapie, welche gegen das Prostataspezifische Membranantigen (PSMA) gerichtet sind, werden bereits im klinischen Alltag angewendet. Weitere potenzielle Biomarker des Prostatakarzinoms, wie beispielsweise der CXC-Motiv-Chemokinrezeptor 4 (CXCR4) und der Somatostatinrezeptor Typ 2 (SSTR2), werden zudem als nuklearmedizinische Zielstrukturen diskutiert. Vorangegangene Arbeiten legten einen Zusammenhang zwischen dem Ausmaß der PSMA-Expression und der Sensitivität gegenüber Docetaxel in Prostatakarzinomzellen nahe. Ein Ziel der vorliegenden Arbeit war, diesen Mechanismus genauer zu untersuchen. Dabei wurden die Aktivität onkogener Signalwege, die Proliferation und die CXCR4- sowie die Androgenrezeptor (AR)- Expression in Prostatakarzinomzelllinien mit unterschiedlicher PSMA-Expression durchflusszytometrisch quantifiziert. Im zweiten Projektteil sollte der Einfluss von Metformin und verschiedener, bereits in der Prostatakarzinomtherapie angewandter Medikamente (Docetaxel, Dexamethason, Abirateron und Enzalutamid), auf die Expression von PSMA, CXCR4 und SSTR2 untersucht werden. Die Quantifizierung der Expression erfolgte mittels Durchflusszytometrie. Ein kausaler Mechanismus für den Zusammenhang zwischen PSMA-Expression und Docetaxel-Sensitivität konnte in dieser Arbeit schließlich nicht hergestellt werden. Es zeigten sich jedoch vor allem Expressionsmodulationen von PSMA und CXCR4. Mittels Docetaxel konnte z.B. bei C4-2 Zellen eine Verdopplung der PSMA-Expression und eine Verdreifachung der CXCR4-Expression erreicht werden. Darüber hinaus zeigte die Behandlung mit Abirateron eine deutliche Heraufregulation der PSMA- Expression bei LNCaP und C4-2 Zellen, sowie eine Zunahme der CXCR4- Expression bei allen untersuchten Zelllinien. Sollte sich der Einfluss der medikamentösen Behandlung auf die Expression von PSMA und CXCR4 bestätigen, kann dies zukünftig zur verbesserten und individualisierten Diagnostik und Therapie von Prostatakarzinompatienten beitragen.
N2 - Nuclear medicine methods are becoming increasingly relevant for the clinical management of prostate carcinoma. Imaging and therapy directed against the prostate specific membrane antigen (PSMA) are already used in clinical practice. Other potential biomarkers of prostate cancer, such as CXC motif chemokine receptor 4 (CXCR4) and somatostatin receptor type 2 (SSTR2), are also being discussed as nuclear medicine targets. Previous work suggested a relationship between the level of PSMA expression and sensitivity to docetaxel in prostate cancer cells. One aim of the present work was to further investigate this mechanism. The activity of oncogenic signalling pathways, proliferation and CXCR4 expression as well as androgen receptor (AR) expression in prostate carcinoma cell lines with different PSMA expression were quantified by flow cytometry. In the second part of the study, the influence of metformin and various drugs already used in prostate carcinoma therapy (docetaxel, dexamethasone, abiraterone and enzalutamide) on the expression of PSMA, CXCR4 and SSTR2 was assessed. Expression was quantified by flow cytometry analysis. A causal mechanism for the connection between PSMA expression and docetaxel sensitivity could, eventually, not be established in this work. However, expression modulations were primarily found for PSMA and CXCR4. Using docetaxel, for instance, a doubling of PSMA expression and a tripling of CXCR4 expression could be achieved in C4-2 cells. In addition, treatment with abiraterone showed a significant upregulation of PSMA expression in LNCaP and C4-2 cells, as well as an increase in CXCR4 expression in all cell lines examined. If the influence of drug treatment on the expression of PSMA and CXCR4 is confirmed, this may contribute to improved and individualised diagnostics and therapy of prostate cancer patients.
KW - Prostatakrebs
KW - Docetaxel
KW - Dexamethason
KW - Metformin
KW - Nuklearmedizin
KW - PSMA
KW - CXCR4
KW - SSTR2
KW - Akt
KW - ERK1/2
KW - p38
KW - Abirateron
KW - Enzalutamid
KW - LNCaP
KW - PC3
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283364
ER -
TY - THES
A1 - Böser, Janis
T1 - Einfluss der PSMA-PET/CT auf das psychische Befinden von Patienten mit Prostatakarzinom
T1 - Emotional state of patients with prostate cancer during PSMA-PET/CT
N2 - Das frühzeitige Erkennen psychoonkologischer Belastungen ist Bestandteil des optimalen therapeutischen Managements von Tumorpatienten. Nur wenige, widersprüchliche Studien untersuchten bisher das psychische Befinden im Verlauf einer PET/CT. Bezogen auf das Prostatakarzinom gibt es bislang keine spezifische Studie, obwohl es die häufigste onkologische Erkrankung des Mannes darstellt. Aufgrund der insgesamt guten Prognose wird von einer geringeren psychischen Belastung ausgegangen. Mithilfe dieser Studie sollte durch Kombination etablierter Fragebögen das psychische Befinden im Verlauf der PET/CT explorativ untersucht werden.
Von Oktober 2018 bis Februar 2020 wurde 531 männlichen Patienten der Nuklearmedizin des Universitätsklinikums Würzburg die Teilnahme angeboten. N = 85 Patienten (n = 38 Patienten mit Prostatakarzinom sowie n = 47 Patienten mit anderen malignen Erkrankungen) stimmten einer vollständigen Teilnahme zu. Es wurden zwei Messzeitpunkte (T1 nach Durchführung der PET/CT; T2 nach Ergebnismitteilung) festgelegt. Als Messinstrumente wurden der PA-F-KF, QUICC, DT, STAI-X1, PANAS und ein Selbsteinschätzungsbogen verwendet.
24 % (T1) bzw. 35 % (T2) der Patienten mit Prostatakarzinom gaben eine dysfunktionale Progredienzangst an, 55 % (T1+T2) eine pathologische psychische Belastung. 53 % (T1) bzw. 50 % (T2) der Patienten zeigten eine relevant erhöhte Zustandsangst.
Die Progredienzangst stieg nach Ergebnismitteilung an (p = 0,048; η² = 0,106), die Ungewissheit über den Stand der Erkrankung (p = 0,014; η² = 0,165) und Bewältigbarkeit des Alltags (p = 0,016; η² = 0,163) reduzierten sich. Allgemeine Ängste wie die Zustandsangst, der Distress und negative Affekte veränderten sich nicht. PSA-Werte ohne bildmorphologisches Korrelat lösten eine größere Unsicherheit bezüglich des aktuellen Krankheitszustandes aus (p = 0,029; η² = 0,128). Jüngere Patienten zeigten vor (p = 0,005; η² = 0,207) und nach (p = 0,001; η² = 0,290) Ergebnismitteilung eine höhere Angst um ihre Berufstätigkeit und gaben eine geringere Erleichterung nach Ergebnismitteilung (p = 0,016; η² = 0,165) an.
Als Limitationen sind die geringe Fallzahl und Teilnahmequote, multiple Testung und fehlende Erfragung psychischer Erkrankungen zu beachten.
Insgesamt zeigen sich eine hohe psychische Belastung und Ängste im Verlauf der PET/CT. Patienten mit Prostatakarzinom sind zu diesem Zeitpunkt nicht weniger belastet als Patienten mit anderen malignen Erkrankungen.
N2 - Early recognition of anxiety and distress is part of an optimal therapeutic management of cancer patients. So far, only a few and contradictory studies have examined psychological well-being during PET/CT. Until now there has been no specific study on prostate cancer, even though it is the most common oncological disease in men. Due to the overall good prognosis, it is assumed that anxiety and distress are lower than in other malignant diseases. This study was intended to examine the psychological well-being after PET/CT and the announcement of the results by combining established questionnaires.
From October 2018 to February 2020, 531 male patients at the department of Nuclear Medicine of the University Hospital Wuerzburg were offered participation. N = 85 patients (n = 38 patients with prostate cancer and n = 47 patients with other malignant diseases) agreed to participate fully. Two measurement times were defined (T1 after the PET/CT was carried out; T2 after the results were reported). The PA-F-KF, QUICC, DT, STAI-X1, PANAS and a self-assessment questionnaire have been used as measuring instruments.
24% (T1) and 35% (T2) of patients with prostate cancer reported dysfunctional fear of progression, 55% (T1+T2) reported pathological distress. 53% (T1) and 50% (T2) of the patients showed relevant levels of anxiety.
Fear of progression increased after the results (p = 0.048; η² = 0.106), uncertainty about the status of the disease (p = 0.014; η² = 0.165) and the ability to cope with everyday life (p = 0.016; η² = 0.163) decreased. General fears such as state anxiety, distress and negative affect did not change.
PSA values without a morphological correlate caused greater uncertainty regarding the current disease status (p = 0.029; η² = 0.128). Younger patients showed greater anxiety about their job before (p = 0.005; η² = 0.207) and after (p = 0.001; η² = 0.290) the result and reported less relief after the announcement of the results (p = 0.016; η² = 0.165).
Limitations that should be taken into account are a small number of cases based on a low participation rate, multiple testing and the lack of information about mental illnesses.
Overall, there is a high level of distress and anxiety during the course of PET/CT. At this point, patients with prostate cancer are no less burdened than patients with other malignancies.
KW - Angst
KW - PET/CT
KW - Anxiety
KW - Prostatakrebs
KW - Nuklearmedizin
KW - Psychoonkologie
KW - Prostatakarzinom
Y1 - 2024
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-352046
ER -
TY - THES
A1 - Kleinert, Kathrin
T1 - Einfluss der thyreostatischen Therapie auf den Erfolg einer Radioiod-Ersttherapie bei der Autoimmunthyreopathie vom Typ M. Basedow
T1 - Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves`disease
N2 - Ziel vorliegender Studie war die Einflussfaktoren der Radioiodtherapie bei der Autoimmunthyreopathie vom Typ M. Basedow insbesondere im Hinblick auf die prätherapeutische thyreostatische Therapie aufgrund der unklaren Datenlage zu erfassen. Der Einfluss von Geschlecht, Alter, Schilddrüsenvolumen, applizierter Aktivität, erzielter Dosis, Uptake und verschiedener Laborparameter, wie TSH, fT3, fT4 wurde untersucht. Aus einem Kollektiv von 465 Patienten konnten 283 als Ersttherapierte identifiziert werden und weitern uni-und multivariater Analyse unterzogen werden. Als Therapieerfolg definiertn wir Patienten, deren TSH- Spiegel ohne Medikation im Normbereich lag, als auch jene, die unabhängig vom TSH-Spiegel nach Radioiodidtherapie eine hypothyreote Stoffwechsellage aufwiesen und substituiert werden mussten. Die Erfolgsquote betrug 86,6%. Unsere Ergebnisse der univariaten Analyse erlauben den Schluss, dass sowohl die erzielte Dosis, das Schilddrüsenvolumen, die applizierte Aktivität, sowie der Uptake relevante Einflussfaktoren einer Radioiodtherapie sind. Die simultane thyreostatische Therapie zeigte weder in uni- noch multivariater Analyse signifikante Unterschiede bezüglich einer erfolgreichen Radioiodtherapie. Eine um 5% niedrigere Erfolgsrate unter simultaner Thyreostase, sowie die Ergebnisse multivariater Betrachtungen deuten jedoch auf einen tendentiellen Einfluss hin. Als Konsequenz für die routinemässige Durchführung einer Radioiodtherapie erscheint es sinnvoll, in Einzelfällen die thyreostatische Medikation frühzeitig vor einer Radioiodtherapie abzusetzen. Eine Beurteilung hinsichtlich des Langzeiterfolges sollte frühestens nach 1 Jahr erfolgen.
N2 - There is a controversy over the factors that may influence the outcome of radioiodine therapy in Graves` disease. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves` disease. In a longitudinal study we assessed the influence of sex, age, antithyroid drugs, target mass, uptake, target radiation dose, applied activity, delivered dose, TSH, fT3, fT4 levels on the outcome of radioiodine therapy. 283 patients (237 female, 46 male) suffering from Graves` disease were entered in the study and followed up until 24 months after therapy. Treatment was defined successful when the TSH level was found to be normal or elevated. 245 patients were successfully treated. Univariate analysis showed the factors target mass, applied activity and delivered dose influencing the outcome of radioiodine therapy. Forward stepwise multiple regression analysis models retained only the delivered dose and the target mass as significantly associated with the outcome of therapy. Antithyroid medication showed a tendency in influencing the result but no significant result. Whereas concomitant antithyroid medication had no significant influence in Graves` disease. This factor only showed a tendency. Conclusion of this longitudinal study was an interruption of concomitant antithyroid medication before a radioiodine therapy can be agreed and the total result can be predicted only one year after radioiodine therapy.
KW - Radioiodtherapie
KW - M. Basedow
KW - Autoimmunthyreopathie
KW - thyreostatischen Therapie
KW - radioiodine therapy
KW - Graves´ disease
KW - antithyroid therapy
Y1 - 2004
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-11759
ER -
TY - THES
A1 - Bögelein, Anna
T1 - Einfluss systemischer Therapeutika auf die CXCR4-Expression von Myelomzellen
T1 - Influence of therapeutic agents on CXCR4 expression of myeloma cells
N2 - Im Zuge der Bemühungen um neue, tumorspezifische Therapieansätze für die Myelomerkrankung hat sich der C-X-C-Chemokinrezeptor 4 (CXCR4) aufgrund seiner zentralen Rolle in der Tumorgenese als vielversprechender Angriffspunkt hervorgetan. Im Sinne eines theranostischen Konzepts wird der Rezeptor mithilfe eines radioaktiv markierten Liganden quantifiziert und anschließend von rezeptorspezifischen Radiotherapeutika als Zielstruktur genutzt. Die CXCR4-Expression ist allerdings ein höchst dynamischer Prozess mit großer inter- und intraindividueller Heterogenität, der u.a. durch eine begleitende Chemotherapie beeinflusst werden kann. Ob sich therapieinduzierte Veränderungen der Rezeptorexpression gezielt nutzen lassen, um die CXCR4-Expression zu optimieren und so die Effektivität der CXCR4-gerichteten Strategien zu steigern, wurde bislang nicht untersucht.
Vor diesem Hintergrund wurden in der vorliegenden Arbeit verschiedene, in der Myelomtherapie etablierte Substanzen sowohl einzeln als auch in Kombination hinsichtlich ihres Einflusses auf die CXCR4-Expression von MM-Zelllinien und primären MM-Zellen unter in vitro Bedingungen analysiert.
In den durchgeführten Experimenten zeigte sich eine hohe Variabilität der CXCR4-Expression der MM-Zellen nach Therapieinduktion, die sich als substanz-, dosis- und zeitabhängig herausstellte. Die Ergebnisse bestätigten das große Potenzial der therapieinduzierten Modulation der CXCR4-Expression. Im weiteren Verlauf sind translationale Forschungsansätze gerechtfertigt, die die Übertragbarkeit der in vitro gewonnenen Ergebnisse auf die komplexen Vorgänge im lebenden Organismus überprüfen. Langfristiges Ziel ist der Entwurf eines patientenzentrierten, multimodalen Therapiekonzepts, welches das CXCR4-gerichtete theranostische Konzept mit einer individuell angepassten, medikamentösen MM-Therapie kombiniert.
N2 - In the course of developing new tumor specific therapeutic approaches for non-yet curable myeloma disease C-X-C chemokine receptor 4 (CXCR4) has emerged as a promising target due to its crucial role in myeloma tumorigenesis. Within a theranostic concept CXCR4 is quantified using radioactively labeled ligands and afterwards targeted by receptor-specific radiopharmaceuticals. However, CXCR4 expression is a very dynamic process with a high inter- and intraindividual heterogeneity which can be influenced by concomitant chemotherapy. Whether therapy induced changes in receptor expression can be used to enhance CXCR4 expression and thus to improve efficacy of CXCR4-based theranostics has not been examined so far.
In this context the present study evaluated the effect of several anti-myeloma drugs (bortezomib, cyclophosphamide, dexamethasone, doxorubicin, lenalidomide) on CXCR4 expression of different human myeloma cell lines as well as patient-derived CD138+ plasma cells under in vitro conditions.
Findings disclosed a high variability of CXCR4 expression on myeloma cells after drug application which turned out to be substance-, dose- and time-dependent. The results confirmed the high potential of therapy-induced modulation of CXCR4 expression. In further course, translational research approaches are justified to verify the transferability of the in vitro findings to the complex macro- and microenvironment in vivo. Long-term goal is the development of a patient-centered, multimodal therapy concept which combines CXCR4 based theranostics with a personalized drug-based therapy.
KW - Plasmozytom
KW - In vitro
KW - Multiples Myelom
KW - Theranostik
KW - CXCR4
KW - Gallium-68 Pentixafor
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241746
ER -
TY - THES
A1 - Omert, Leilah Marie-Luise
T1 - Einfluss systemischer Therapie auf die funktionelle Bildgebung des Multiplen Myeloms
T1 - Influence of systemic therapy on functional imaging of Multiple Myeloma
N2 - Das Multiple Myelom (MM) ist eine maligne hämatologische Erkrankung, die trotz großer Fortschritte in der Therapie immer noch eine schlechte Prognose hat.
Bisher ist es nicht möglich, mit einem bildgebenden Verfahren alle Fragen der Diagnostik, der Stadieneinteilung, des Therapiemonitorings und der Evaluation der Prognose des Multiplen Myeloms zu klären. Da es sich beim Multiplen Myelom aber um eine stark heterogene Erkrankung handelt, die eine frühzeitige individuelle Therapie erfordert, ist es unbedingt nötig Verfahren zu entwickeln, die eine spezifische Charakterisierung der Erkrankung bei jedem einzelnen Patienten ermöglichen.
In der vorliegenden Arbeit wurden die MM-Zelllinien INA-6, MM.1S und OPM-2 mit dem Proteasominhibitor MLN9708 behandelt. Behandelte und unbehandelte Zellen wurden mit dem Standardtracer 2-[18F]-Fluoro-2-Desoxy-D-Glukose (18F-FDG) oder dem in der Anwendung beim Multiplen Myelom neuen Aminosäuretracer [11C]-Methionin (11C-MET) inkubiert und die Aufnahme der Tracer zu bestimmten Zeitpunkten gemessen. Des Weiteren wurde die Ausprägung biologischer Merkmale der MM-Pathogenese bei behandelten und unbehandelten Zellen untersucht. Anschließend wurde ermittelt, ob ein Zusammenhang zwischen der Höhe der Traceraufnahme und der Ausprägung biologischer Merkmale der MM-Pathogenese bei behandelten und unbehandelten Zellen besteht.
Hierdurch soll geklärt werden, ob 11C-MET besser zur Diagnostik, dem Therapiemonitoring und der Evaluation der Prognose des Multiplen Myeloms geeignet ist als der Standardtracer 18F-FDG.
Es zeigte sich eine signifikant höhere 11C-MET-Aufnahme sowohl unbehandelter als auch behandelter Zellen im Vergleich zu 18F-FDG. Außerdem war eine Unterscheidung zwischen behandelten und unbehandelten Zellen mit 11C-MET besser möglich als mit 18F-FDG. Zwischen Traceraufnahme und biologischen Merkmalen der MM-Pathogenese, wie Proliferation, Expression von intrazellulären Leichtketten, CXCR4 und CD138, ergaben sich für behandelte und unbehandelte Zellen variable Zusammenhänge.
Die Ergebnisse legen nahe, dass 11C-MET besser zur Diagnostik und zum Therapiemonitoring des Multiplen Myeloms geeignet ist als der Standardtracer 18F-FDG.
Ob 11C-MET auch zur Stadieneinteilung und zur Evaluation der Prognose des Multiplen Myeloms besser geeignet ist als 18F-FDG, muss in weiteren Studien untersucht werden.
N2 - Despite new therapies Multiple Myeloma (MM) remains a hematologic malignancy with poor prognosis. Because of marked disease heterogeneity outcomes are extremely variable. The role of functional imaging, such as positron emission tomography for diagnosis, therapy monitoring, staging and prognostication is being investigated for a few years. This study evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for diagnosis, therapy monitoring, staging and outcome prediction of MM. Influence of proteasome-inhibitor MLN9708 (Ixazomib) on radiotracer-uptake of different MM cell-lines was analyzed and related to tumor-biology. Both untreated and treated MM cells significantly took up more 11C-Methionine than 18F-FDG. Discrimination of treated and untreated cells was only possible with 11C-Methionine. Correlations between tracer uptake and tumor biology were variable for both tracers. These results suggest that 11C-Methionine is superior to 18F-FDG in diagnosis and therapy monitoring of MM. The suitability of 11C-Methionine for staging and prognostication has to be evaluated in further studies.
KW - Multiples Myelom
KW - Bildgebung
KW - PET
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154793
ER -
TY - THES
A1 - Becker, Kilian
T1 - Entwicklung eines 3D-Ganzkörper-Ultraschalls an Kleintieren für morphologische Bildgebung, Volumetrie und Bildfusion mit PET
T1 - Development of a 3D whole-body ultrasound in small animals for morphological imaging, volumetry and image fusion with PET
N2 - Einleitung: Ultraschall wird seit mehr als 50 Jahren in der Medizin eingesetzt und ist mittlerweile ein unverzichtbares diagnostisches Verfahren, es erlaubt eine nicht-invasive Darstellung der Morphologie und Funktion von Organen in Echtzeit. In der Kleintierbildgebung dominieren bisher zur morphologischen Bildgebung Computertomographie (CT) und Magnetresonanztomographie (MRT). Daher wurde in der vorliegenden Arbeit die Idee entwickelt, die morphologischen Informationen des 3D-Ultraschalls (3D-US) für Untersuchungen an Kleintieren zu verwenden, außerdem sollten Methoden zur multimodalen Bildgebung und Bildfusion von 3D-US und Kleintier-Positronenemissionstomographie (PET) entwickelt werden. Der Vorteil des Ultraschalls gegenüber dem Kleintier-CT liegt in der fehlenden Strahlenbelastung und der guten Verfügbarkeit, was besonders für Verlaufsstudien von Interesse ist. Methoden und Ergebnisse: Zur Bildoptimierung wurde ein Fadenphantom entwickelt, welches aufgrund der feinen Strukturen die qualitative als auch quantitative Bestimmung der Auflösung ermöglicht. Die Vorarbeiten am Fadenphantom konnten exzellent die Probleme des 3D-Ultraschalls mit der achsenabhängigen Auflösung zeigen und ermöglichten eine schnelle Beurteilung der Bildqualität. Hier bestehen Einsatzmöglichkeiten in der Bewertung verschiedener Ultraschallgeräte bezüglich der Tauglichkeit für 3D-Datenaquisition. Zur reproduzierbaren Lagerung von Mäusen wurde eine Schallkopfführung ein sowohl für 3D-US als auch Kleintier-PET kompatibler Tierhalter entwickelt. Die Maus lag zur Untersuchung im angewärmten Wasserbad auf dem Tierhalter fixiert, mit Inhalationsanästhesie und Sauerstoff über eine Atemmaske versorgt. Der Zeitaufwand für eine 3D-US-Untersuchung betrug für die Akquisition etwa eine Minute. Die generierten Ultraschalldatensätze waren von guter Qualität, Strukturen wie Leber, Nieren, Blase, Wirbelsäule und Lunge konnten selbst bei kleinen Mäusen von unter 20 Gramm Körpergewicht gut dargestellt werden. Zur Validierung des 3D-Ultraschalls wurde das Volumen verschiedener Organe und Tumore bestimmt und mit dem Goldstandard verglichen. Um die Koregistrierung mit der Kleintier-PET zu ermöglichen, wurden auf dem Tierhalter drei „fiducial markers“ angebracht, die Position und Orientierung eindeutig definieren. Die Kleintier-PET-Untersuchungen wurden nach standardisierten Protokollen durchgeführt. Die anschließende Bildfusion erfolgte mittels der frei verfügbaren Software "Amide". Diskussion: Mit dem in dieser Arbeit beschriebenen Verfahren ist eine standardisierte Gewinnung von 3D-US-Datensätzen an Kleintieren möglich; zusätzlich konnte die Machbarkeit der Bildfusion mit PET-Datensätzen gezeigt werden. Der Einsatz des 3D-Ultraschalls in longitudinalen Studien, zum Beispiel zur Beurteilung der Tumorprogression, ist vorstellbar. Die Zuverlässigkeit der volumetrischen Berechnungen ist für größere Organvolumina gut, bei kleineren Volumina besteht noch Optimierungsbedarf. Weitere Verbesserungen könnten durch den Einsatz von speziellen Schallköpfen und höheren Schallfrequenzen erzielt werden.
N2 - Introduction: Ultrasound has been used for more than 50 years in medicine and has become a indispensable diagnostic tool, it allows a non-invasive imaging of the morphology and function of organs in real time. Small animal morphological imaging is now dominated by CT and MRI. For present study the idea to use morphological information of the 3D-ultrasound for examination of small animals was developed, these data should be used for image fusion of 3D ultrasound and small-animal PET. The advantage of ultrasound compared to the small-animal CT is the lack of radiation exposure and the good availability, which is especially for longitudinal studies of interest. Methods and Results: For image enhancement, a thread phantom was developed, fine structures facilitate qualitative and quantitative analysis of spatial resolution. Preliminary work on the thread phantom was excellent for investigate problems of 3D ultrasound with the axis-dependent resolution. There are potential applications for evaluating different ultrasonic devices in their suitability for 3D data acquisition. For the reproducible bedding of mice a guide bar for ultrasound transducer and a compatible holder for 3D-US and PET was developed. The mouse was bedded in the heated water bath fixed to the holder, applied inhalation anesthesia and oxygen through a breathing mask. The time required for a 3D ultrasound examination was for the acquisition of about one minute. The generated ultrasound data sets were of good quality, structures such as liver, kidney, bladder, spine and lungs were even in the case of small mice of 20 gram well represented. For validation of the 3D ultrasound volumes of various organs and tumors were determined and compared with gold standard. To allow coregistration with the microPET, three "fiducial markers" were attached to define the position and orientation. PET studies were performed according to standardized protocols. The subsequent image fusion was performed using the software "amide”. Discussion: In this study a standardized procedure for 3D-US of small animals was developed, in addition, the feasibility of image fusion with PET data sets was shown. The use of 3D ultrasound in longitudinal studies, for example, to assess tumor progression, is conceivable. The reliability of the volumetric calculations is good for large organ volumes, with smaller volumes, there is still need for improvement. Further improvements could be achieved through the use of special transducers and higher ultrasound frequencies.
KW - Ultraschalldiagnostik
KW - Nuklearmedizin
KW - Würzburg / Klinik und Poliklinik für Nuklearmedizin
KW - Molekulare Bildgebung
KW - 3D-Ultraschall
KW - dreidimensionaler Ultraschall
KW - PET
KW - Positronenemissionstomographie
KW - Bildfusion
KW - 3D ultrasound
KW - three-dimensional ultrasound
KW - PET
KW - positron emission tomography
KW - image fusion
Y1 - 2010
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-55916
ER -
TY - THES
A1 - Schadt, Fabian
T1 - Entwicklung und erste Validierung eines innovativen Analysen-Tools für präklinische Bewertungen von PET-Radiopharmazeutika zur \(in\) \(vivo\) Untersuchungen neurologischer Erkrankungen
T1 - Development and initial validation of an innovative analytical tool for preclinical evaluations of PET radiopharmaceuticals for \(in\) \(vivo\) investigations of neurological disease
N2 - Die präklinische Forschung stellt den ersten wichtigen Meilenstein in der Klärung und Untersuchung klinisch-relevanter Erkrankungen dar. Darüber hinaus unterstützt die präklinische Forschung erheblich die Entwicklung von Therapien. Die Kleintier-Positronenemissionstomographie (µ-PET) spielt dabei eine wichtige Rolle, da sie in der Lage ist, funktionelle, physiologische und biochemische Prozesse in vivo darzustellen und zu quantifizieren. Trotz diverser etablierter PET-Datenauswertungs-Programme bleibt die Analyse von in vivo akquirierten Bilddaten aufgrund der Vielzahl an medizinischen Fragestellungen, der Komplexität der Krankheitsbilder, sowie der Etablierung neuer Radiotracer weiterhin eine große Herausforderung in der Medizin. Ziel dieser Doktorarbeit ist es daher, ein geeignetes, brauchbares Auswertungstool für eine einfache und effiziente Analyse von akquirierten µ-PET-Daten zu entwickeln und zu etablieren, welches das Spektrum bereits vorhandener Programme erweitert. Das entwickelte nuklearmedizinische Datenverarbeitungs-Analyseprogramm (engl. nuclear medicine data processing analysis tool, NU_DPA) wurde in Matlab implementiert und anhand dreier präklinischer Versuchs- bzw. Testreihen erprobt und etabliert. Bei den Datenreihen handelt es sich um µ-PET-Datensätze verschiedener Schlaganfall-Rattenhirnmodelle unter Verwendung folgender Radiotracer. Zum einen die im Gehirn homogen akkumulierende 2-[18F]Fluor-2-desoxy-glukose ([18F]FDG) zum anderen das spezifisch an P-Selektin anreichernde [68Ga]Fucoidan.
Das NU_DPA umfasst die automatische Selektion des Zielvolumens (volume-of-interest, VOI) aus dem vollständigen PET-Bild und die anschließende Ausrichtung des VOI mit Hilfe eines PET-Templates (gemittelter PET-Datensatz). Dieses PET Template wird aus den eigenen akquirierten PET-Daten erstellt. Durch das Einbinden eines geeigneten anatomischen MRT-Atlas‘ (anpassbar) können die ausgerichteten PET-Daten einzelnen, Atlas-spezifischen Teilregionen zugeordnet werden. Eine solche Subklassifikation des VOI erlaubt eine genauere Betrachtung und Auswertung der Radiotracer-Akkumulation.
Des Weiteren bietet NU_DPA die Möglichkeit einer semiquantitativen Auswertung der PET-Bilddaten anhand von drei unterschiedlichen Parametern, der normalisierten Aktivität, dem Standardized Uptake Value und der Uptake Ratio. Durch die Matlab-integrierten Statistik-Algorithmen ist zusätzlich eine Möglichkeit der statistischen Auswertung der zuvor berechneten Parameter gegeben. Das NU_DPA-Programm stellt somit ein semi-automatisiertes Datenauswertungs-Programm dar, das sowohl die Registrierung als auch die semiquantitative Auswertung von PET-Bilddaten innerhalb einer Versuchsreihe ermöglicht und bereits erfolgreich für die Radiotracer [18F]FDG und [68Ga]Fucoidan in Tiermodellen getestet wurde. Nach derzeitigem Kenntnisstand ist kein Datenauswertungs-Programm bekannt, das PET-Bilddaten unter Verwendung des hinzugefügten Atlas‘ semi-automatisiert analysieren kann und potenziell für homogene und Target-spezifisch akkumulierende Radiotracer geeignet ist.
N2 - Preclinical research represents the first important milestone in the clarification and investigation of clinically relevant diseases. In addition, preclinical research significantly supports the development of therapies. Small animal positron emission tomography (µ-PET) plays an important role in this context, as it is able to image and quantify functional, physiological and biochemical processes in vivo. Despite various established µ-PET data analysis programs, the analysis of in vivo acquired image data remains a major challenge in medicine due to the multitude of medical questions, the complexity of disease patterns, and the establishment of new radiotracers. Therefore, the aim of this PhD thesis is to develop and establish a suitable, usable evaluation tool for a simple and efficient analysis of acquired µ-PET data, which extends the spectrum of already existing programs. The developed nuclear medicine data processing analysis tool (NU_DPA) was implemented in Matlab and tested and established on the basis of three preclinical experimental or test series. The data series are µ-PET datasets of different stroke rat brain models using the following radiotracers:
2-[18F]fluoro-2-deoxy-glucose ([18F]FDG), which accumulates homogeneously in the brain and [68Ga]fucoidan, which specifically accumulates at p-selectin.
The NU_DPA involves automatic segmentation of a volume-of-interest (VOI) from the full PET image and the subsequent alignment of the VOI using a PET template (averaged PET dataset). This PET template is created from the own acquired PET data. By embedding a suitable anatomical MR atlas (customizable), the aligned PET data can be assigned to individual atlas-specific sub-regions. Such a sub-classification of the VOI allows a more detailed analysis and evaluation of the radiotracer accumulation.
Furthermore, NU_DPA offers the possibility of a semi-quantitative evaluation of the PET image data based on three different parameters, the normalized activity, the standardized uptake value and the uptake ratio. The Matlab-integrated statistical algorithms provide an additional option for statistical evaluation of the previously calculated semi-quantitative parameters. The NU_DPA program thus represents a semi-automatic data evaluation program that enables both the registration and the semi-quantitative evaluation of PET image data within a series of experiments and it has already been successfully tested for the radiotracers [18F]FDG and [68Ga]fucoidan in animal models. To the best of our current knowledge, there is no known data analysis program that can semi-automatically analyze PET image data using the added atlas and is potentially suitable for homogeneous and target-specific accumulating radiotracers.
KW - PET
KW - Präklinische Bildgebung
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-247499
ER -
TY - THES
A1 - Page, Lukas
T1 - Entwicklung und präklinische Evaluation immunologischer und nuklearmedizinischer diagnostischer Tests für Schimmelpilz-assoziierte Hypersensitivität und invasive Mykosen
T1 - Development and preclinical evaluation of immunological and nuclear medical diagnostic assays for mould-associated hypersensitivity and invasive mycoses
N2 - Schimmelpilze können in Abhängigkeit des Immunstatus und der Vorerkrankungen betroffener Patienten unterschiedliche Krankheitsbilder wie Hypersensitivitäts-erkrankungen oder lebensbedrohliche invasive Infektionen hervorrufen. Da die Diagnosestellung dieser Erkrankungen mitunter komplex und insensitiv ist, sollten im Rahmen dieser Arbeit unterschiedliche Ansätze neuer diagnostischer Assays untersucht werden.
In den letzten Jahren wurden Assays entwickelt, die auf Basis durchflusszytometrisch quantifizierter Pilz-spezifischer T-Zellen aus peripherem Blut einen supportiven Biomarker zur Diagnostik invasiver Mykosen liefern könnten. Da die hierfür isolierten T-Zellen anfällig gegenüber präanalytischer Lagerzeiten und immunsuppressiver Medikation sind, wurden hier Protokolloptimierungen vorgenommen, um anhand eines Vollblut-basierten Assays mit zusätzlicher CD49d-Kostimulation diesen Limitationen entgegen zu wirken. In einer Studie an gesunden Probanden konnte dabei gezeigt werden, dass die Kombination der Durchflusszytometrie mit ausgewählten Zytokin-Messungen (IL-5, IL-10 und IL-17) zu einer verbesserten Erkennung vermehrt Schimmelpilz-exponierter Personen beitragen könnte. Neben Infektionen könnten dabei im umwelt- und arbeitsmedizinischen Kontext Polarisationen der T-Zell-Populationen detektiert werden, welche mit Sensibilisierungen und Hypersensitivität assoziiert werden.
Zusätzlich wurde ein in vitro Transwell® Alveolarmodell zur Simulation pulmonaler Pilzinfektionen für Erreger der Ordnung Mucorales adaptiert, durch Reproduktion wichtiger Merkmale der Pathogenese von Mucormykosen validiert, und für Untersuchungen der Immunpathologie und Erreger-Invasion verwendet. Das Modell wurde anschließend zur in vitro Evaluation von radioaktiv markiertem Amphotericin B mit 99mTc oder 68Ga als nuklearmedizinischen Tracer verwendet. Die untersuchten Schimmelpilze zeigten dabei eine zeit- und dosis-abhängige Aufnahme der Tracer, während bakteriell infizierte Proben nicht detektiert wurden. Die erhobenen Daten dokumentieren ein vielversprechendes Potenzial von Amphotericin B-basierten Tracer, das in zukünftigen in vivo Studien weiter evaluiert werden sollte.
N2 - Depending on the immune constitution and predisposing illnesses, moulds can cause a variety of diseases ranging from hypersensitivity syndromes to life-threatening invasive infections. As the diagnosis of mould-associated diseases remains challenging, this work aimed to refine immunological assays and to develop molecular imaging protocols for pulmonary mould infections.
Recently, a flow cytometric assay for mould specific T cell quantification has been proposed as a novel supportive biomarker to diagnose invasive mycoses. As these assays are susceptible to pre-analytic delays and immunosuppressive drugs, a whole blood-based protocol with enhanced CD28 plus CD49d co-stimulation was developed and was shown to be less prone to these limitations. In addition, a study on healthy volunteers demonstrated the applicability of flow cytometric antigen-reactive T cell quantification as a surrogate of environmental mould exposure, especially when combined with T-cellular cytokine measurements (specifically, IL-5, IL-10, and IL-17). Therefore, these assays could potentially be used to detect polarizations of T-cell populations associated with sensitization and hypersensitivity, e. g. in allergology and occupational medicine.
Moreover, an in vitro Transwell® alveolar model of invasive pulmonary mould infections has been adapted to study mucormycoses, validated by recapitulation of known pathogenicity factors, and used to characterize the immunopathology and epithelial invasion of Mucorales. The Transwell® model was subsequently used to evaluate radioactively labelled Amphotericin B with either 99mTc or 68Ga as a potential nuclear medical tracer. Time- and dose-dependent enrichment of the tracers was found in both Aspergillus and Mucorales, whereas samples infected with bacteria showed negligible uptake. These in vitro data document a promising potential of radiolabeled amphotericin B for molecular imaging of invasive mycoses and encourage further evaluation in animal models.
KW - Schimmelpilze
KW - Diagnostik
KW - Biomarker
KW - Tracer
KW - Zellkultur
KW - Antimykotika
KW - Mucorales
KW - Aspergillus
KW - T-Zellen
KW - Immunsuppressiva
KW - Antifungal
KW - Mucormycosis
KW - Aspergillosis
KW - T cells
KW - Immunosuppressant
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252459
ER -
TY - THES
A1 - Juhran, Nina
T1 - Epidemiologie des Iodmangels im Würzburger Raum: Schilddrüsenvolumina und Iodausscheidung bei Schulkindern in Würzburg
T1 - epidemiology of iodine deficiency in the area of wuerzburg: thyroid volume and ioduresis of children in wuerzburg
N2 - Deutschland gilt bisher immer noch als Iodmangelgebiet, obwohl in der letzten Zeit einige Studien eine deutliche Verbesserung der Iodversorgung in der deutschen Bevölkerung zeigten. Allerdings wurde der Großteil dieser Untersuchungen nicht gemäß den epidemiologischen Kriterien der WHO, UNICEF und ICCIDD durchgeführt, was zu einem Selektionsbias im Hinblick auf die Einschätzung der Strumaprävalenz führte. Die ideale Zielgruppe für die Beurteilung der aktuellen Iodversorgung einer Population sind Kinder im Schulalter zwischen 7 und 17 Jahren, weil die kindliche Schilddrüse sehr viel empfindlicher auf Veränderungen in der Iodzufuhr reagiert, und Schulkinder leicht in großer Zahl repräsentativ untersucht werden können. Gleichzeitig werden dabei auch verschiedene soziale Bevölkerungsschichten abgedeckt. An der Würzburger Studie nahmen 591 Kinder teil. Dabei handelte es sich um 268 Mädchen und 323 Jungen im Alter von 7 bis 17 Jahren. Es wurden folgende Daten erhoben: Schilddrüsenvolumen mit Hilfe der Sonographie, Iodkonzentration im morgendlichem Mittelstrahlurin, Körpergewicht, Größe, Geschlecht und Alter. Der Median der Iodkonzentration im Urin lag bei 183 µg/L. Der Anteil an Urinproben mit Iodkonzentrationen unter 100µg/L bzw. unter 50µg/L betrug 15,4% (Ziel nach WHO: <50%) bzw. 4,3% (Ziel nach WHO: <20%). 17,3 % der Proben enthielten hohe Konzentrationen über 300µg/L. Damit sind alle Kriterien der WHO hinsichtlich einer ausreichenden Iodzufuhr erfüllt. Der Grund für diese deutliche Verbesserung ist zum einen darin zu sehen, daß fast alle Familien ( 97%) im Haushalt Iodsalz verwenden und 19,6% aller Kinder regelmäßig Iodtabletten einnehmen. Zum anderen basiert die mittlerweile normale Iodversorgung wohl hauptsächlich auf dem fast ausschließlichen Einsatz von Iodsalz in der Lebensmittelindustrie (Bäcker und Metzger). In Bezug auf die Referenzwerte der Schilddrüsenvolumina der WHO/ICCIDD ergab sich für die Würzburger Schulkinder eine Strumaprävalenz von 0,2%, sowohl in Relation zu Alter und Geschlecht, als auch zu Körperoberfläche und Geschlecht. Im Vergleich mit den 97. Perzentilen der ursprünglichen Normdaten von Gutekunst und Martin-Teichert errechnete sich wie statistisch zu erwarten war eine Kropfhäufigkeit von 3%. Damit sind die Schilddrüsenvolumina der Würzburger Schulkinder vergleichbar mit den aktuellen Werten von Kindern mit ausreichender Iodversorgung sowohl aus der Schweiz, als auch aus dem Raum Berlin und Leipzig. Deutschland ist deshalb wahrscheinlich nicht länger als ein Land mit einer Iodmangelsituation anzusehen, wenngleich diese Daten durch weitere flächendeckende Studien an Kindern untermauert werden müssen. Die Würzburger Untersuchung und die meisten der anderen aktuell veröffentlichten Studien an Schulkindern mit ausreichender Iodversorgung geben zudem Grund zur Annahme, daß die Referenzwerte der WHO/ICCIDD für die Schilddrüsenvolumina zu hoch angesetzt sind, was mittlerweile von Seiten der WHO korrigiert wird.
N2 - Germany still is an area of iodine deficiency, although a lot of studies have shown that there is a significant improvement of the iodine supply. In this study we examined the thyroid volume and the ioduresis of children -according to the guidelines of the WHO- in the age of 7 to 18, because they show the current iodine supply. The results reveal that Wuerzburg is no longer an area of iodine deficieny, because the thyroid volumes of the children in Wuerzburg are smaller than postulated by the WHO and with a ioduresis of 183 µg/L iodine there is no longer a sign of iodine deficiency.
KW - Würzburg
KW - Schulkind
KW - Iodmangel
KW - Iod
KW - Iodmangel
KW - Schilddrüsenvolumen
KW - iodine
KW - iodine deficiency
KW - thyroid volume
Y1 - 2003
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-5643
ER -
TY - THES
A1 - Hartrampf, Philipp Emanuel
T1 - Evaluation der PET-Tracer [\(^1\)\(^8\)F]FDG, [\(^1\)\(^8\)F]Cholin und [\(^6\)\(^8\)Ga]PSMA I&T zur nicht-invasiven Charakterisierung von Prostatakarzinomzellen und des Ansprechens auf eine Docetaxeltherapie
T1 - Evaluation of PET tracers [\(^1\)\(^8\)F]FDG, [\(^1\)\(^8\)F]choline and [\(^6\)\(^8\)Ga]PSMA I&T for non-invasive characterization of prostate cancer cells and response to docetaxel therapy
N2 - Das Prostatakarzinom (PCa) stellt derzeit in Deutschland die häufigste Krebserkrankung der männlichen Bevölkerung dar und steht bei den tödlich verlaufenden Malignomen an zweiter Stelle. Aktuell umfasst die Diagnostik immer öfter auch eine molekulare Bildgebung mittels PET/CT und den Tracern [18F]Cholin und [68Ga]PSMA. Letzterer detektiert selektiv das prostataspezifische Membranantigen (PSMA), welches in Prostatakarzinomzellen häufig überexprimiert ist. Das Wachstum von PCa geschieht in der Regel androgenabhängig, wobei sich auch teilweise eine androgenunabhängige Entwicklung findet. Für das bei kastrationsresistenten Karzinomen und fortgeschrittenen Stadien eingesetzte Chemotherapeutikum Docetaxel, werden immer wieder Resistenzentwicklungen beobachtet, wodurch dieses nur unzureichend effektiv ist. Ziel dieser Arbeit war es, die Eignung verschiedener PET-Tracer ([18F]FDG, [18F]Cholin und [68Ga]PSMA) zur Bildgebung androgenabhängiger und -unabhängiger Prostatakarzinomzellen zu testen sowie ihr Potential zur Beurteilung des Therapieansprechens auf Docetaxel zu untersuchen. Weiterhin sollte untersucht werden, ob die [68Ga]PSMA-Retention mit der PSMA-Expression korreliert. Im zweiten Teil wurde ein Zusammenhang zwischen der Expression von PSMA und der Resistenzentwicklung gegen Docetaxel untersucht.
Methoden: Für die in-vitro Experimente wurden die hormonabhängige Zelllinie LNCaP sowie die hormonunabhängige Zelllinie LNCaP C4-2 verwendet. Im zweiten Teil wurden zusätzlich PSMA-negative PC-3 Zellen eingesetzt. Die aufgenommene bzw. gebundene Traceraktivität wurde mittels Gammacounter gemessen. Die Untersuchung der PSMA-Expression erfolgte mit Western-Blot und Durchflusszytometrie. Ein PSMA-Knockdown-System wurde mittels siRNA in LNCaP-Zellen etabliert.
Ergebnisse: Die PSMA-Expression und die Sensitivität gegenüber Docetaxel waren bei LNCaP Zellen tendenziell erhöht gegenüber der LNCaP C4-2 Zelllinie. Nach Docetaxelbehandlung zeigte sich in beiden Zellreihen eine unveränderte PSMA-Expression. Der PSMA-spezifische PET-Tracer zeigte, im Vergleich zu den metabolischen Tracern [18F]FDG und [18F]Cholin, eine nur sehr geringe Retention. Im Vergleich der Zelllinien untereinander nahmen LNCaP C4-2 Zellen ca. 50 % mehr [18F]FDG auf als LNCaP Zellen. Die Aufnahme von [18F]Cholin unterschied sich nicht signifikant. Der Tracer [68Ga]PSMA zeigte eine höhere Bindung an LNCaP Zellen im Vergleich zu LNCaP C4-2 Zellen. In weiteren Versuchen konnte gezeigt werden, dass sowohl [18F]FDG als auch [18F]Cholin, nicht jedoch [68Ga]PSMA in vitro ein Therapieansprechen auf Docetaxel durch verminderte Traceraufnahme in beiden Zelllinien aufzeigen. Es konnte zudem eine direkte Korrelation zwischen der [68Ga]PSMA-Bindung und der PSMA-Expression nachgewiesen werden.
Nach einer siRNA-vermittelten Verminderung der PSMA-Expression in LNCaP Zellen (Knockdown-Zellen) zeigte sich eine deutlich geringere Sensitivität für Docetaxel. Gleichzeitig war jedoch die Docetaxelsensitivität von PSMA-negativen PC-3 Zellen höher als die von LNCaP Knockdown-Zellen.
Schlussfolgerung: Insgesamt zeigten unsere Untersuchungen, dass sich die PET-Tracer [18F]FDG und [68Ga]PSMA zur Unterscheidung des androgenabhängigen Zellmodells vom androgenunabhängigen Modell eignen. Außerdem ermöglicht der [68Ga]PSMA-Tracer eine Einschätzung der PSMA-Expression. Die Tracer [18F]FDG und [18F]Cholin eignen sich in vitro für die Beurteilung des Therapieansprechens einer Docetaxeltherapie, [68Ga]PSMA dagegen nicht. Die PSMA-Expression scheint ein entscheidender, aber nicht alleinstehender Faktor für die Sensitivität von LNCaP Zellen gegenüber Docetaxel zu sein. Es scheinen hierbei allerdings eher der Verlust von PSMA, wie im Knockdown-Modell induziert, sowie bislang unbekannte Faktoren eine wichtige Rolle zu spielen.
N2 - Prostate carcinoma (PCa) is currently the most frequent cancer in men in Germany and is the second leading cause of cancer deaths. Currently, diagnostics more and more often include molecular imaging using PET/CT and the tracers [18F]choline and [68Ga]PSMA. The latter selectively detects the prostate-specific membrane antigen (PSMA), which is often overexpressed in prostate cancer cells. The growth of PCa is usually androgen-dependent, although it is sometimes also developing independently of androgen. For the chemotherapeutic agent docetaxel, which is used for castration-resistant carcinomas and advanced stages, the development of resistance is observed again and again, resulting in insufficient efficacy. The aim of this work was to evaluate the potential of different PET tracers ([18F]FDG, [18F]Choline and [68Ga]PSMA) for the imaging of androgen-dependent and independent prostate carcinoma cells as well as their potential for the assessment of therapy response to docetaxel. Furthermore, it should be investigated whether [68Ga]PSMA uptake correlates with PSMA expression. In the second part, an association between the expression of PSMA and the development of resistance to docetaxel was investigated.
Methods: For the in vitro experiments the hormone-dependent cell line LNCaP and the hormone-independent cell line LNCaP C4-2 were used. In the second part PSMA-negative PC-3 cells were additionally used. The tracer uptake and binding activity was measured by gamma counter. PSMA expression was determined by Western blot and flow cytometry. A PSMA knockdown system was established in LNCaP cells using siRNA.
Results: PSMA expression and sensitivity to docetaxel were increased in LNCaP cells compared to the LNCaP C4-2 cells. After docetaxel treatment, both cell lines showed unchanged PSMA expression. Compared to the metabolic tracers [18F]FDG and [18F]choline, the PSMA-specific PET tracer showed very low uptake. In comparison of the cell lines, LNCaP C4-2 cells took up about 50 % more [18F]FDG than LNCaP cells. The uptake of [18F]choline did not differ significantly. The tracer [68Ga]PSMA showed a higher binding to LNCaP cells compared to LNCaP C4-2 cells. In further experiments it was observed that both [18F]FDG and [18F]choline, but not [68Ga]PSMA, in vitro showed a therapy response to docetaxel by reduced tracer uptake in both cell lines. A direct correlation between [68Ga]PSMA binding and PSMA expression was also found.
After a siRNA-mediated reduction of PSMA expression in LNCaP cells (knockdown cells), a significantly lower sensitivity for docetaxel was observed. At the same time, however, the docetaxel sensitivity of PSMA-negative PC-3 cells was higher than that of LNCaP knockdown cells.
Conclusion: Overall, our investigations showed that the PET tracers [18F]FDG and [68Ga]PSMA are suitable for differentiating the androgen-dependent cell model from the androgen-independent model. In addition, the [68Ga]PSMA tracer allows an assessment of PSMA expression. The tracers [18F]FDG and [18F]choline are suitable for in vitro assessment of response to docetaxel therapy, whereas [68Ga]PSMA is not. PSMA expression seems to be a critical, but not unique, factor for the sensitivity of LNCaP cells to docetaxel. However, the loss of PSMA, as induced in the knockdown model, as well as unknown factors seem to play an important role.
KW - Positronen-Emissions-Tomografie
KW - PSMA
KW - [18]F-Cholin
KW - [68]Ga-PSMA I&T
KW - Docetaxel
KW - LNCaP
KW - [18]F-choline
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176299
ER -
TY - JOUR
A1 - Hendricks, Anne
A1 - Lenschow, Christina
A1 - Kroiss, Matthias
A1 - Buck, Andreas
A1 - Kickuth, Ralph
A1 - Germer, Christoph-Thomas
A1 - Schlegel, Nicolas
T1 - Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery
JF - Langenbeck's Archives of Surgery
N2 - Purpose
Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse.
Methods
A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated.
Results
Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%.
Conclusion
These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.
KW - Primary hyperparathyroidism (pHPT)
KW - preoperative localization
KW - repeat surgery
KW - diagnostics
KW - imaging
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267520
SN - 1435-2451
VL - 406
IS - 5
ER -
TY - JOUR
A1 - Selcuk, Nalan Alan
A1 - Toklu, Turkay
A1 - Beykan, Seval
A1 - Karaaslan, Serife Ipek
T1 - Evaluation of the dosimetry approaches in ablation treatment of thyroid cancer
JF - Journal of Applied Clinical Medical Physics
N2 - In this study, we aimed to evaluate dosimetric approaches in ablation treatment of Differentiated Thyroid Carcinoma (DTC) without interrupting the clinical routine. Prior to therapy, 10.7 MBq 131I in average was orally given to 24 patients suffering from DTC. MIRD formalism was used for dosimetric calculations. For blood and bone marrow dosimetry, blood samples and whole-body counts were collected at 2, 24, 72, and 120 h after I-131 administration. For remnant tissue dosimetry, uptake measurements were performed at the same time intervals. To estimate the remnant volume, anterior and lateral planar gamma camera images were acquired with a reference source within the field of view at 24 h after I-131 administration. Ultrasound imaging was also performed. Treatment activities determined with the fixed activity method were administered to the patients. Secondary cancer risk relative to applied therapy was evaluated for dosimetric approaches. The average dose to blood and bone marrow were determined as 0.15 ± 0.04 and 0.11 ± 0.04 Gy/GBq, respectively. The average remnant tissue dose was 0.58 ± 0.52 Gy/MBq and the corresponding required activity to ablate the remnant was approximately 1.3 GBq of 131I. A strong correlation between 24th-hour uptake and time-integrated activity coefficient values was obtained. Compared to fixed activity method, approximately five times higher secondary cancer risk was determined in bone marrow dosimetry, while the risk was about three times lower in lesion-based dosimetry.
KW - bone marrow dosimetry
KW - remnant tissue dosimetry
KW - thyroid ablation treatment
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235882
VL - 19
ER -
TY - THES
A1 - Andermann, Paul
T1 - Evaluierung der Intra- und Interobserver-Variabilität bei der 2D-Ultraschall-Schilddrüsenvolumetrie an einem Schilddrüsenphantom - Vergleich zu 3D-Ultraschall-Referenzmessungen an gesunden Probanden
N2 - Mehrere Autoren haben schon die Intra- und Interobserver-Variabilität bei der Bestimmung des Schilddrüsenvolumens und knotiger Herdbefunde mit Hilfe des zweidimensionalen (2D) Ultraschalls evaluiert. Darüber hinaus wurde über Interobserver-Korrelationen für Schilddrüsenvolumenmessungen berichtet. Es gibt jedoch keine prospektive verblindete Studie, die die Intra- bzw. Interobserver-Variabilität bei der Volumenbestimmung der gesamten Schilddrüse an gesunden Probanden bzw. einzelner Knoten unterschiedlicher Echogenität an einem Phantom untersucht hat. Die Ergebnisse der Einzelstudien sollen hier vorgestellt und – soweit möglich – miteinander verglichen werden. Im Rahmen einer quantitativen Studie mit dem hier präsentierten Schilddrüsenphantom soll die Intra- und Interobserver-Variabilität bei der 2D-Ultraschallvolumetrie einzelner Knoten unterschiedlicher Größe und Echogenität und der Schilddrüsenlappen evaluiert werden. Da Schilddrüsenknoten wegen des geringeren Volumens und ihrer oft unscharfen Randkontur schwieriger zu entdecken und auszumessen sind als die Gesamtschilddrüse, soll untersucht werden, welche Größenordnungen des Messfehlers auftreten und in welcher Relation sie zueinander stehen. Außerdem soll der methodenimmanente Fehler quantifiziert und detektierbare Volumenänderungen erfassbar gemacht werden. Bisher war in der Schilddrüsensonographie kein geeignetes Phantom verfügbar, das kommerziell erhältlich ist und mit dem qualitativ unterschiedliche intrathyreoidale Herdbefunde untersucht werden können. Die vorliegende Studie an gesunden Probanden hatte das primäre Ziel, die Frage nach der Quantifizierbarkeit von Unsicherheitsfaktoren in der Schilddrüsenvolumetrie durch den konventionellen 2D-Ultraschall im Vergleich zu 3D-Referenzvolumina bei gesunden Erwachsenen möglichst exakt zu beantworten und die Untersucherabhängigkeit der Methode zu demonstrieren. Damit soll die Genauigkeit (Richtigkeit und Präzision) der sonographischen Schilddrüsendiagnostik mathematisch erfasst und eine bessere Bewertungsgrundlage für die Frage nach der Reproduzierbarkeit von Ultraschall-Volumenbestimmungen der Schilddrüse und ihrer pathologischen Veränderungen geschaffen werden. Hierfür wurden möglichst aussagekräftige statistische Parameter wie die Intra- und Interobserver-Variabilität, der systematische und zufällige Fehler, der reine Fehler der Messmethode, minimale, sicher detektierbare Volumenänderungen und im Rahmen einer multivariaten Reliabilitätsanalyse die Reliabilitätskoeffizienten untersucht. Ein weiteres Ziel dieser Studie bestand darin, die Reliabilität der in der klinischen Routine benutzten Ellipsoidformel zur Berechnung des Schilddrüsenvolumens zu überprüfen.
KW - Intraobserver-Variabilität
KW - Interobserver-Variabilität
KW - Ultraschall
KW - Schilddrüsenvolumetrie
KW - Schilddrüsenphantom
Y1 - 2007
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-23434
ER -