14868
2015
eng
8418-8429
10
6
article
1
2017-05-17
--
--
\(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
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.
Oncotarget
10.18632/oncotarget.3053
urn:nbn:de:bvb:20-opus-148688
Oncotarget, 2015, 6(10), 8418-8429. DOI: 10.18632/oncotarget.3053
Katharina Lückerath
Constantin Lapa
Christa Albert
Ken Herrmann
Gerhard Jörg
Samuel Samnick
Herrmann Einsele
Stefan Knop
Andreas K. Buck
eng
uncontrolled
positron emission tomography
eng
uncontrolled
imaging techniques
eng
uncontrolled
experience
eng
uncontrolled
\(^{11}\)C-Methionine-PET
eng
uncontrolled
treatment response
eng
uncontrolled
molecular imaging
eng
uncontrolled
multiple myeloma
eng
uncontrolled
management
eng
uncontrolled
\(^{18}\)F-FDG PET/CT
eng
uncontrolled
bone disease
eng
uncontrolled
stem-cell transplantation
eng
uncontrolled
esophagogastric junction
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14868/038_Lueckerath_Oncotarget.pdf
16998
2017
eng
96732-96737
57
8
article
1
2018-10-25
--
--
Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma.
Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up.
Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed.
In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.
Oncotarget
10.18632/oncotarget.18235
29228566
urn:nbn:de:bvb:20-opus-169989
Oncotarget, 2017, Vol. 8, No. 57, 96732-96737. DOI: 10.18632/oncotarget.18235
false
true
Constantin Lapa
Stefan Kircher
Andreas Schirbel
Andreas Rosenwald
Saskia Kropf
Theo Pelzer
Thorsten Walles
Andreas K. Buck
Wolfgang A. Weber
Hans-Juergen Wester
Ken Herrmann
Katharina Lückerath
eng
uncontrolled
PET
eng
uncontrolled
CXCR4
eng
uncontrolled
[\(^{68}\)Ga] pentixafor
eng
uncontrolled
pleural mesothelioma
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Medizinische Klinik und Poliklinik I
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16998/010_Lapa_ONCOTARGET.pdf
17731
2016
eng
41233-41241
27
7
article
1
2019-02-26
--
--
The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy
Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.
Oncotarget
10.18632/oncotarget.9775
urn:nbn:de:bvb:20-opus-177318
Oncotarget 2016, 7:27, 41233-41241. DOI: 10.18632/oncotarget.9775
false
true
Rudolf A. Werner
Seval Beykan
Takahiro Higuchi
Katharina Lückerath
Alexander Weich
Michael Scheurlen
Christina Bluemel
Ken Herrmann
Andreas K. Buck
Michael Lassmann
Constantin Lapa
Heribert Hänscheid
eng
uncontrolled
renal scintigraphy
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
177Lu
eng
uncontrolled
MAG3
eng
uncontrolled
PRRT
Pharmakologie, Therapeutik
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17731/Werner_Oncotarget.pdf
12549
2015
eng
e0122269
3
10
article
1
2016-01-26
--
--
Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?
Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
Methods
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
Results
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
Conclusion
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
PLoS One
10.1371/journal.pone.0122269
urn:nbn:de:bvb:20-opus-125498
PLoS ONE 10(3): e0122269. doi:10.1371/journal.pone.0122269
Constantin Lapa
Thomas Linsenmann
Katharina Lückerath
Samuel Samnick
Ken Herrmann
Carolin Stoffer
Ralf-Ingo Ernestus
Andreas K. Buck
Mario Löhr
Camelia-Maria Monoranu
eng
uncontrolled
glioma
eng
uncontrolled
positron emission tomography
eng
uncontrolled
glioblastoma multiforme
eng
uncontrolled
macrophages
eng
uncontrolled
somatostatin
eng
uncontrolled
microglial cells
eng
uncontrolled
immunostaining
eng
uncontrolled
magnetic resonance imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12549/Lapa_journal.pone.0122269.pdf
11310
2014
eng
article
1
2015-05-11
--
--
18FDG-PET/CT for prognostic stratification of patients with multiple myeloma relapse after stem cell transplantation
The aim of this study was to investigate the prognostic value of 18F-fluoro-deoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) in 37 patients with a history of multiple myeloma (MM) and suspected or confirmed recurrence after stem cell transplantation (SCT). All patients had been heavily pre-treated. Time to progression (TTP) and overall survival (OS) were correlated to a number of different PET-derived as well as clinical parameters. Impact on patient management was assessed.
Absence of FDG-avid MM foci was a positive prognostic factor for both TTP and OS (p<0.01). Presence of >10 focal lesions correlated with both TTP (p<0.01) and OS (p<0.05). Interestingly, presence of >10 lesions in the appendicular skeleton proved to have the strongest association with disease progression. Intensity of glucose uptake and presence of extramedullary disease were associated with shorter TTP (p=0.037 and p=0.049, respectively). Manifestations in soft tissue structures turned out to be a strong negative predictor for both, TTP and OS (p<0.01, respectively). PET resulted in a change of management in 30% of patients.
Our data underline the prognostic value of 18F-FDG-PET/CT in MM patients also in the setting of post-SCT relapse. PET/CT has a significant impact on patient management.
urn:nbn:de:bvb:20-opus-113107
OncoTarget 5 (2014),17, S. 7381-7391
Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW)
Katharina Lückerath
Constantin Lapa
Uwe Malzahn
Samuel Samnick
Herrmann Einsele
Andreas K. Buck
Ken Herrmann
Stefan Knop
eng
uncontrolled
18FDG-PET/CT
eng
uncontrolled
Multiple myeloma
eng
uncontrolled
molecular imaging
eng
uncontrolled
FDG-PET/CT
Medizin und Gesundheit
open_access
Institut für Medizinische Strahlenkunde und Zellforschung
Medizinische Klinik und Poliklinik II
Institut für Klinische Epidemiologie und Biometrie
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11310/124_Herrmann_Oncotarget.pdf
11131
2013
eng
article
1
2015-03-19
--
--
Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology
Purpose
Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[11C]-methionine (11C-MET) and [18F]-fluoroethyl-L-tyrosine (18F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity.
Experimental Design
To study the utility of 11C-MET, 18F-Fet and 18F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138+ plasma cells were characterized regarding uptake and biomedical features.
Results
Using myeloma cell lines and patient-derived CD138+ plasma cells, we found that the relative uptake of 11C-MET exceeds that of 18F-FDG 1.5- to 5-fold and that of 18F-Fet 7- to 20-fold. Importantly, 11C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of 11C-MET.
Conclusion
These data suggest that 11C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with 18F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.
10.1371/journal.pone.0084840
urn:nbn:de:bvb:20-opus-111319
PLoS ONE 8(12): e84840. doi:10.1371/journal.pone.0084840
Katharina Lückerath
Constantin Lapa
Annika Spahmann
Gerhard Jörg
Samuel Samnick
Andreas Rosenwald
Herrmann Einsele
Stefan Knop
Andreas Buck
eng
uncontrolled
Myelomas
eng
uncontrolled
Antibodies
eng
uncontrolled
Positron emission tomography
eng
uncontrolled
Myeloma cells
eng
uncontrolled
cell staining
eng
uncontrolled
lesions
eng
uncontrolled
biosynthesis
eng
uncontrolled
bone marrow cells
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Medizinische Klinik und Poliklinik II
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11131/024_Lueckerath_PLoS.pdf
11061
2014
eng
article
1
2015-02-27
--
--
Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy
Background
Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused.
Methods
Twenty-two patients undergoing PRRT with standard activities of 177Lu-DOTATATE/-TOC were monitored during two following treatment cycles with co-infusion of 75 and 50 g of AA (L-arginine and L-lysine), respectively. Mean serum levels of potassium and other parameters (glomerular filtration rate [GFR], creatinine, blood urea nitrogen [BUN], phosphate, chloride, lactate dehydrogenase) prior to, 4 h and 24 h after AA infusion were compared.
Results
Self-limiting hyperkalaemia (>5.0 mmol/l) resolving after 24 h occurred in 91% (20/22) of patients in both protocols. Potassium levels, BUN, creatinine, GFR, phosphate, chloride and LDH showed a similar range at 4 h after co-infusion of 75 or 50 g of AA, respectively (p > 0.05). Only GFR and creatinine levels at 24 h varied significantly between the two co-infusion protocols (p < 0.05).
Conclusions
Hyperkalaemia is a frequent side effect of AA infusion in PRRT. Varying the dose of co-infused amino acids did not impact on the incidence and severity of hyperkalaemia.
10.1186/s13550-014-0046-2
urn:nbn:de:bvb:20-opus-110617
EJNMMI Research 2014, 4:46. doi:10.1186/s13550-014-0046-2
Rudolf A. Werner
Constantin Lapa
Christina Bluemel
Katharina Lückerath
Andreas Schirbel
Alexander Strate
Andreas K. Buck
Ken Herrmann
eng
uncontrolled
NET
eng
uncontrolled
PRRT
eng
uncontrolled
Hyperkalaemia
eng
uncontrolled
Arginine
eng
uncontrolled
Lysine
Medizin und Gesundheit
open_access
Institut für Klinische Biochemie und Pathobiochemie
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11061/120_Werner_EJNMMI.pdf
17209
2017
eng
1589-1597
6
7
article
1
2018-11-19
--
--
CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
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.
Theranostics
10.7150/thno.19050
28529638
urn:nbn:de:bvb:20-opus-172095
Theranostics (2017) 7:6, pp. 1589-1597. https://www.thno.org/v07p1589.htm
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Ken Herrmann
Andreas Schirbel
Heribert Hänscheid
Katharina Lückerath
Margret Schottelius
Malte Kircher
Rudolf A. Werner
Martin Schreder
Samuel Samnick
Saskia Kropf
Stefan Knop
Andreas K. Buck
Hermann Einsele
Hans-Juergen Wester
K. Martin Kortüm
eng
uncontrolled
medicine
eng
uncontrolled
multiple myeloma
eng
uncontrolled
PET
eng
uncontrolled
CXCR4
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17209/Lapa_v07p1589.pdf
17210
2017
eng
205-212
1
7
article
1
2018-11-19
--
--
[\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
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.
Theranostics
10.7150/thno.16576
28042328
urn:nbn:de:bvb:20-opus-172106
Theranostics (2017) 7:1, pp. 205-212. https://www.thno.org/v07p0205.htm
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Martin Schreder
Andreas Schirbel
Samuel Samnick
Klaus Martin Kortüm
Ken Herrmann
Saskia Kropf
Herrmann Einsele
Andreas K. Buck
Hans-Jürgen Wester
Stefan Knop
Katharina Lückerath
eng
uncontrolled
medicine
eng
uncontrolled
multiple myeloma
eng
uncontrolled
FDG
eng
uncontrolled
molecular imaging
eng
uncontrolled
CXCR4
eng
uncontrolled
PET
eng
uncontrolled
radionuclide therapy
eng
uncontrolled
theranostics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17210/Lapa_v07p0205.pdf
14873
2015
eng
477-487
4
7
article
1
2017-05-17
--
--
In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
EMBO Molecular Medicine
10.15252/emmm.201404698
urn:nbn:de:bvb:20-opus-148738
EMBO Molecular Medicine 7(4), 477-487 (2015). DOI: 10.15252/emmm.201404698
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Kathrin Philipp-Abbrederis
Ken Herrmann
Stefan Knop
Margret Schottelius
Matthias Eiber
Katharina Lückerath
Elke Pietschmann
Stefan Habringer
Carlos Gerngroß
Katharina Franke
Martina Rudelius
Andreas Schirbel
Constantin Lapa
Kristina Schwamborn
Sabine Steidle
Elena Hartmann
Andreas Rosenwald
Saskia Kropf
Ambros J Beer
Christian Peschel
Hermann Einsele
Andreas K Buck
Markus Schwaiger
Katharina Götze
Hans-Jürgen Wester
Ulrich Keller
eng
uncontrolled
FDG PET/CT
eng
uncontrolled
cells
eng
uncontrolled
CXCR4/SDF-1
eng
uncontrolled
CXCR4
eng
uncontrolled
multiple myeloma
eng
uncontrolled
positron emission tomography
eng
uncontrolled
chemokine receptor
eng
uncontrolled
in vivo imaging
eng
uncontrolled
malignancies
eng
uncontrolled
involvement
eng
uncontrolled
microenvironment
eng
uncontrolled
survival
eng
uncontrolled
cancer
eng
uncontrolled
autologous transplantation
eng
uncontrolled
bone disease
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14873/043_Philipp-Abbrederis_EMBO_Molecular_Medicine.pdf
16817
2016
eng
428-434
3
6
article
1
2018-09-12
--
--
\(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
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.
Theranostics
10.7150/thno.13986
urn:nbn:de:bvb:20-opus-168174
Theranostics 2016, Vol. 6, Issue 3, 428-434. DOI: 10.7150/thno.13986
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Katharina Lückerath
Irene Kleinlein
Camelia Maria Monoranu
Thomas Linsenmann
Almuth F. Kessler
Martina Rudelius
Saskia Kropf
Andreas K. Buck
Ralf-Ingo Ernestus
Hans-Jürgen Wester
Mario Löhr
Ken Herrmann
eng
uncontrolled
imaging
eng
uncontrolled
chemokine receptor-4
eng
uncontrolled
glioblastoma
eng
uncontrolled
positron emission tomography/computed tomography
eng
uncontrolled
\(^{68}\)Ga-Pentixafor
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16817/Lapa_Theranostics.pdf
17967
2016
eng
8
11
article
1
2019-04-24
--
--
Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging
Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and –testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.
PLoS ONE
10.1371/journal.pone.0160282
urn:nbn:de:bvb:20-opus-179678
PLoS ONE 2016, 11(8):e0160282. DOI:10.1371/journal.pone.0160282
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
David Fecher
Elisabeth Hofmann
Andreas Buck
Ralph Bundschuh
Sarah Nietzer
Gudrun Dandekar
Thorsten Walles
Heike Walles
Katharina Lückerath
Maria Steinke
eng
uncontrolled
lung and intrathoracic tumors
eng
uncontrolled
trachea
eng
uncontrolled
adenocarcinoma of the lung
eng
uncontrolled
cancer treatment
eng
uncontrolled
secondary lung tumors
eng
uncontrolled
pulmonary imaging
eng
uncontrolled
extracellular matrix
eng
uncontrolled
collagens
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Thorax-, Herz- u. Thorakale Gefäßchirurgie
Klinik und Poliklinik für Nuklearmedizin
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17967/Fecher_Plos_One.pdf
17203
2017
eng
2956-2964
11
7
article
1
2018-11-16
--
--
\(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions
\(^{11}\)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.
Theranostics
10.7150/thno.20491
28824728
urn:nbn:de:bvb:20-opus-172038
Theranostics (2017) 7:11, pp. 2956-2964. https://doi.org/10.7150/thno.20491
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Maria J. Garcia-Velloso
Katharina Lückerath
Samuel Samnick
Martin Schreder
Paula Rodriguez Otero
Jan-Stefan Schmid
Ken Herrmann
Stefan Knop
Andreas K. Buck
Hermann Einsele
Jesus San-Miguel
Klaus Martin Kortüm
eng
uncontrolled
medicine
eng
uncontrolled
PET/CT
eng
uncontrolled
\(^{11}\)C-methionine
eng
uncontrolled
multiple myeloma
eng
uncontrolled
FDG
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17203/Lapa_v07p2956.pdf