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 - 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 - JOUR
A1 - Brumberg, Joachim
A1 - Blazhenets, Ganna
A1 - Schröter, Nils
A1 - Frings, Lars
A1 - Jost, Wolfgang H.
A1 - Lapa, Constantin
A1 - Meyer, Philipp T.
T1 - Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators
JF - EJNMMI Physics
N2 - Background
The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible.
Methods
We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure.
Results
H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6%).
Conclusions
The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.
KW - MIBG
KW - collimator
KW - heart-to-mediastinum ratio
KW - linear conversion
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221675
VL - 6
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 - 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 - 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 - Chen, Xinyu
A1 - Kudo, Takashi
A1 - Lapa, Constantin
A1 - Buck, Andreas
A1 - Higuchi, Takahiro
T1 - Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements
JF - Journal of Neural Transmission
N2 - The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used \(^{123/131}\)I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. \(^{11}\)C-HED and \(^{18}\)F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed.
KW - norepinephrine transporter
KW - benzylguanidine
KW - phenethylguanidine
KW - antidepressant
KW - organic cation transporter
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241148
VL - 127
ER -
TY - JOUR
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Javadi, Mehrbod S.
A1 - Maya, Yoshifumi
A1 - Decker, Michael
A1 - Lapa, Constantin
A1 - Herrmann, Ken
A1 - Higuchi, Takahiro
T1 - Radionuclide imaging of neurohormonal system of the heart
JF - Theranostics
N2 - Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included.
KW - SPECT
KW - radiotracer
KW - heart failure
KW - cardiac neurohormonal system
KW - nuclear cardiology
KW - PET
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149205
VL - 5
IS - 6
ER -
TY - JOUR
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Koshino, Kazuhiro
A1 - Nose, Naoko
A1 - Mühlig, Saskia
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
JF - Theranostics
N2 - Background: Radiolabeled agents that are substrates for the norepinephrine transporter (NET) can be used to quantify cardiac sympathetic nervous conditions and have been demonstrated to identify high-risk congestive heart failure (HF) patients prone to arrhythmic events. We aimed to fully characterize the kinetic profile of the novel \(^{18}\)F-labeled NET probe AF78 for PET imaging of the cardiac sympathetic nervous system (SNS) among various species.
Methods: \(^{18}\)F-AF78 was compared to norepinephrine (NE) and established SNS radiotracers by employing in vitro cell assays, followed by an in vivo PET imaging approach with healthy rats, rabbits and nonhuman primates (NHPs). Additionally, chase protocols were performed in NHPs with NET inhibitor desipramine (DMI) and the NE releasing stimulator tyramine (TYR) to investigate retention kinetics in cardiac SNS.
Results: Relative to other SNS radiotracers, 18F-AF78 showed higher transport affinity via NET in a cell-based competitive uptake assay (IC\(^{50}\) 0.42 ± 0.14 µM), almost identical to that of NE (IC\(^{50}\), 0.50 ± 0.16 µM, n.s.). In rabbits and NHPs, initial cardiac uptake was significantly reduced by NET inhibition. Furthermore, cardiac tracer retention was not affected by a DMI chase protocol but was markedly reduced by intermittent TYR chase, thereby suggesting that \(^{18}\)F-AF78 is stored and can be released via the synaptic vesicular turnover process. Computational modeling hypothesized the formation of a T-shaped π-π stacking at the binding site, suggesting a rationale for the high affinity of \(^{18}\)F-AF78.
Conclusion: \(^{18}\)F-AF78 demonstrated high in vitro NET affinity and advantageous in vivo radiotracer kinetics across various species, indicating that \(^{18}\)F-AF78 is an SNS imaging agent with strong potential to guide specific interventions in cardiovascular medicine.
KW - norepinephrine transporter
KW - T-shaped π-π stacking
KW - nonhuman primates
KW - radiotracer kinetics
KW - cardiac innervation imaging
KW - sympathetic nervous system
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300685
VL - 12
IS - 9
SP - 4446
EP - 4458
ER -
TY - JOUR
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Lapa, Constantin
A1 - Nose, Naoko
A1 - Hirano, Mitsuru
A1 - Javadi, Mehrbod S.
A1 - Robinson, Simon
A1 - Higuchi, Takahiro
T1 - Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195
JF - EJNMMI Research
N2 - Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover.
Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization.
Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.
KW - phaeochromocytoma
KW - Positronen-Emissions-Tomografie
KW - heart failure
KW - sympathetic nervous system
KW - storage vesicle turnover
KW - positron emission tomography
KW - 18F-LMI1195
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167081
SN - 2191-219X
VL - 8
IS - 12
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 - Eissler, Cristoph
A1 - Werner, Rudolf A.
A1 - Arias-Loza, Paula
A1 - Nose, Naoko
A1 - Chen, Xinyu
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
T1 - The number of frames on ECG-gated \(^{18}\)F-FDG small animal PET has a significant impact on LV systolic and diastolic functional parameters
JF - Molecular Imaging
N2 - Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 & PLUSMN; 57.7 mu l*, 380.8 & PLUSMN; 57.2 mu l*, 398.0 & PLUSMN; 63.1 mu l*, and 444.8 & PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.
KW - Myocardial-perfusion SPECT
KW - left-ventricular function
KW - ejection fraction
KW - MRI
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265778
VL - 2021
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Heinrich, Marieke
A1 - Seitz, Anna Katharina
A1 - Brumberg, Joachim
A1 - Sokolakis, Ioannis
A1 - Kalogirou, Charis
A1 - Schirbel, Andreas
A1 - Kübler, Hubert
A1 - Buck, Andreas K.
A1 - Lapa, Constantin
A1 - Krebs, Markus
T1 - Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results?
JF - Journal of Clinical Medicine
N2 - (1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland–Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible.
KW - prostate-specific membrane antigen (PSMA)
KW - metabolic tumour volume (MTV)
KW - total lesion PSMA
KW - biomarker
KW - software
KW - comparability
KW - agreement
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205893
SN - 2077-0383
VL - 9
IS - 5
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 - JOUR
A1 - Hoffmann, Jan V.
A1 - Janssen, Jan P.
A1 - Kanno, Takayuki
A1 - Shibutani, Takayuki
A1 - Onoguchi, Masahisa
A1 - Lapa, Constantin
A1 - Grunz, Jan-Peter
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
T1 - Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging
JF - EJNMMI Physics
N2 - Background
Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)).
Methods
The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison.
Results
Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT\(^+\)) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR.
Conclusions
While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.
KW - small-animal imaging
KW - SPECT
KW - mouse
KW - ollimator
KW - post-reconstruction filtering
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230361
VL - 7
ER -
TY - JOUR
A1 - Hänscheid, Heribert
A1 - Hartrampf, Philipp E.
A1 - Schirbel, Andreas
A1 - Buck, Andreas K.
A1 - Lapa, Constantin
T1 - Intraindividual comparison of [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Purpose
The radiolabelled somatostatin analogue [\(^{177}\)Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [\(^{177}\)Lu]Lu-DOTA-TOC.
Methods
Activity kinetics in organs and tumours after [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy.
Resuluts
In comparison to [\(^{177}\)Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [\(^{177}\)Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [\(^{177}\)Lu]Lu-DOTA-TOC in 4 of 5 patients.
Conclusions
Prior to a treatment with [\(^{177}\)Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.
KW - intraindividual comparison
KW - DOTA-EB-TATE
KW - somatostatin receptor
KW - evans blue
KW - biokinetics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265470
SN - 1619-7089
VL - 48
IS - 8
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 - 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 - 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 - JOUR
A1 - Lapa, Constantin
A1 - Arias-Loza, Paula
A1 - Hayakawa, Nobuyuki
A1 - Wakabayashi, Hiroshi
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Shinaji, Tetsuya
A1 - Herrmann, Ken
A1 - Pelzer, Theo
A1 - Higuchi, Takahiro
T1 - Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus
JF - Scientific Reports
N2 - Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.
KW - molecular medicine
KW - endocrinology
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159066
VL - 7
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 - 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 - Lapa, Constantin
A1 - Kircher, Malte
A1 - Hänscheid, Heribert
A1 - Schirbel, Andreas
A1 - Grigoleit, Götz Ulrich
A1 - Klinker, Erdwine
A1 - Böck, Markus
A1 - Samnick, Samuel
A1 - Pelzer, Theo
A1 - Buck, Andreas K
T1 - Peptide receptor radionuclide therapy as a new tool in treatment-refractory sarcoidosis - initial experience in two patients
JF - Theranostics
N2 - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve virtually all organ systems. Whereas most patients present without symptoms, progressive and disabling organ failure can occur in up to 10% of subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide therapy (PRRT) has recently received market authorization for treatment of SSTR-positive neuroendocrine tumors.
Methods:
We describe the first case series comprising two patients with refractory multi-organ involvement of sarcoidosis who received 4 cycles of PRRT.
Results:
PRRT was well-tolerated without any acute adverse effects. No relevant toxicities could be recorded during follow-up. Therapy resulted in partial response accompanied by a pronounced reduction in pain (patient #1) and stable disease regarding morphology as well as disease activity (patient #2), respectively.
Conclusion:
Peptide receptor radionuclide therapy in sarcoidosis is feasible and might be a new valuable tool in patients with otherwise treatment-refractory disease. Given the long experience with and good tolerability of PRRT, further evaluation of this new treatment option for otherwise treatment-refractory sarcoidosis in larger patient cohorts is warranted.
KW - peptide receptor
KW - PRRT
KW - sarcoidosis
KW - somatostatin receptors
KW - radionuclide therapy
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158983
VL - 8
IS - 3
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Kircher, Stefan
A1 - Schirbel, Andreas
A1 - Rosenwald, Andreas
A1 - Kropf, Saskia
A1 - Pelzer, Theo
A1 - Walles, Thorsten
A1 - Buck, Andreas K.
A1 - Weber, Wolfgang A.
A1 - Wester, Hans-Juergen
A1 - Herrmann, Ken
A1 - Lückerath, Katharina
T1 - Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
JF - Oncotarget
N2 - 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.
KW - PET
KW - CXCR4
KW - [\(^{68}\)Ga] pentixafor
KW - pleural mesothelioma
KW - theranostics
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169989
VL - 8
IS - 57
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Linsenmann, Thomas
A1 - Lückerath, Katharina
A1 - Samnick, Samuel
A1 - Herrmann, Ken
A1 - Stoffer, Carolin
A1 - Ernestus, Ralf-Ingo
A1 - Buck, Andreas K.
A1 - Löhr, Mario
A1 - Monoranu, Camelia-Maria
T1 - Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?
JF - PLoS One
N2 - 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.
KW - glioma
KW - positron emission tomography
KW - glioblastoma multiforme
KW - macrophages
KW - somatostatin
KW - microglial cells
KW - immunostaining
KW - magnetic resonance imaging
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125498
VL - 10
IS - 3
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 - Lapa, Constantin
A1 - Reiter, Theresa
A1 - Kircher, Malte
A1 - Schirbel, Andreas
A1 - Werner, Rudolf A.
A1 - Pelzer, Theo
A1 - Pizarro, Carmen
A1 - Skowasch, Dirk
A1 - Thomas, Lena
A1 - Schlesinger-Irsch, Ulrike
A1 - Thomas, Daniel
A1 - Bundschuh, Ralph A.
A1 - Bauer, Wolfgang R.
A1 - Gartner, Florian C.
T1 - Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI
JF - Oncotarget
N2 - Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR.
15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity.
SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up.
In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively.
Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.
KW - sarcoidosis
KW - PET
KW - SSTR
KW - somatostatin receptor
KW - DOTATOC
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175423
VL - 7
IS - 47
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 - JOUR
A1 - Lapa, Constantin
A1 - Werner, Rudolf A.
A1 - Bluemel, Christina
A1 - Lueckerath, Katharina
A1 - Muegge, Dirk O.
A1 - Strate, Alexander
A1 - Haenscheid, Heribert
A1 - Schirbel, Andreas
A1 - Allen-Auerbach, Martin S.
A1 - Bundschuh, Ralph A.
A1 - Buck, Andreas K.
A1 - Herrmann, Ken
T1 - Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy
JF - EJNMMI Research
N2 - Background
Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0).
Methods
In 38 patients, standard activity of \(^{177}Lu\)-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated.
Results
At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK.
Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37).
Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%).
Conclusions
A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT.
KW - amino acids
KW - kidney function
KW - hyperkalemia
KW - PRRT
KW - NET
KW - MAG3
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124963
VL - 4
IS - 74
ER -
TY - JOUR
A1 - Li, Xiang
A1 - Samnick, Samuel
A1 - Lapa, Constantin
A1 - Israel, Ina
A1 - Buck, Andreas K.
A1 - Kreissl, Michael C.
A1 - Bauer, Wolfgang
T1 - 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors
N2 - Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
KW - Medizin
KW - Atherosclerotic plaque
KW - 68Ga-DOTATATE
KW - Somatostatin receptor
KW - Cardiovascular risk factors
KW - Macrophage
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76231
ER -
TY - JOUR
A1 - Linz, Christian
A1 - Brands, Roman C.
A1 - Kertels, Olivia
A1 - Dierks, Alexander
A1 - Brumberg, Joachim
A1 - Gerhard-Hartmann, Elena
A1 - Hartmann, Stefan
A1 - Schirbel, Andreas
A1 - Serfling, Sebastian
A1 - Zhi, Yingjun
A1 - Buck, Andreas K.
A1 - Kübler, Alexander
A1 - Hohm, Julian
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity – initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Purpose
While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.
Methods
Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference.
Results
[\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples.
Conclusion
FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.
KW - molecular imaging
KW - fibroblast activation protein
KW - head and neck cancer
KW - PET
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307246
SN - 1619-7070
SN - 1619-7089
VL - 48
IS - 12
ER -
TY - JOUR
A1 - Löhr, Mario
A1 - Härtig, Wolfgang
A1 - Schulze, Almut
A1 - Kroiß, Matthias
A1 - Sbiera, Silviu
A1 - Lapa, Constantin
A1 - Mages, Bianca
A1 - Strobel, Sabrina
A1 - Hundt, Jennifer Elisabeth
A1 - Bohnert, Simone
A1 - Kircher, Stefan
A1 - Janaki-Raman, Sudha
A1 - Monoranu, Camelia-Maria
T1 - SOAT1: A suitable target for therapy in high-grade astrocytic glioma?
JF - International Journal of Molecular Sciences
N2 - Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.
KW - SOAT1
KW - glioblastoma
KW - astrocytoma
KW - IDH1/2
KW - lipid droplets
KW - mitotane
KW - targeted therapy
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284178
SN - 1422-0067
VL - 23
IS - 7
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 - Lückerath, Katharina
A1 - Lapa, Constantin
A1 - Malzahn, Uwe
A1 - Samnick, Samuel
A1 - Einsele, Herrmann
A1 - Buck, Andreas K.
A1 - Herrmann, Ken
A1 - Knop, Stefan
T1 - 18FDG-PET/CT for prognostic stratification of patients with multiple myeloma relapse after stem cell transplantation
N2 - 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.
KW - 18FDG-PET/CT
KW - Multiple myeloma
KW - molecular imaging
KW - FDG-PET/CT
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113107
ER -
TY - JOUR
A1 - Lückerath, Katharina
A1 - Lapa, Constantin
A1 - Spahmann, Annika
A1 - Jörg, Gerhard
A1 - Samnick, Samuel
A1 - Rosenwald, Andreas
A1 - Einsele, Herrmann
A1 - Knop, Stefan
A1 - Buck, Andreas
T1 - Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology
N2 - 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.
KW - Myelomas
KW - Antibodies
KW - Positron emission tomography
KW - Myeloma cells
KW - cell staining
KW - lesions
KW - biosynthesis
KW - bone marrow cells
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111319
ER -
TY - JOUR
A1 - Marquardt, André
A1 - Hartrampf, Philipp
A1 - Kollmannsberger, Philip
A1 - Solimando, Antonio G.
A1 - Meierjohann, Svenja
A1 - Kübler, Hubert
A1 - Bargou, Ralf
A1 - Schilling, Bastian
A1 - Serfling, Sebastian E.
A1 - Buck, Andreas
A1 - Werner, Rudolf A.
A1 - Lapa, Constantin
A1 - Krebs, Markus
T1 - Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures
JF - Cancers
N2 - (1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.
KW - machine learning
KW - tumor microenvironment
KW - immune infiltration
KW - angiogenesis
KW - mRNA
KW - miRNA
KW - transcriptome
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305036
SN - 2072-6694
VL - 15
IS - 2
ER -
TY - JOUR
A1 - Matsusaka, Yohji
A1 - Chen, Xinyu
A1 - Arias-Loza, Paula
A1 - Werner, Rudolf A.
A1 - Nose, Naoko
A1 - Sasaki, Takanori
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
T1 - In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats
JF - Molecular Imaging
N2 - Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of % of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of % (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, %; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.
KW - Sodium-Glucose Cotransporters (SGLTs)
KW - diabetes
KW - rats
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300708
VL - 2022
ER -
TY - JOUR
A1 - Matsusaka, Yohji
A1 - Werner, Rudolf A.
A1 - Arias-Loza, Paula
A1 - Nose, Naoko
A1 - Sasaki, Takanori
A1 - Chen, Xinyu
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
T1 - Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals
JF - Molecular Imaging
N2 - Background. Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods. A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing 99mTc-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as , with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [99mTc]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results. In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion. Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.
KW - SPECT Scanner
KW - medium-sized animals
KW - performance
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300713
VL - 2022
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 - 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 - Nose, Naoko
A1 - Werner, Rudolf A.
A1 - Ueda, Yuichiro
A1 - Günther, Katharina
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Fukushima, Kazuhito
A1 - Edenhofer, Frank
A1 - Higuchi, Takahiro
T1 - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
JF - International Journal of Cardiology
N2 - BACKGROUND:
Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay.
MATERIAL AND METHODS:
Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F‑2‑fluoro‑2‑deoxy‑d‑glucose (\(^{18}\)F-FDG) and \(^{125}\)I‑β‑methyl‑iodophenyl‑pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively.
RESULTS:
After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM.
CONCLUSIONS:
During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW - tracer
KW - Stammzelle
KW - induced pluripotent stem cells
KW - cardiomyocytes
KW - fatty acid
KW - stem cell therapy
KW - hiPSC-CM
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170699
VL - 269
ER -
TY - INPR
A1 - Nose, Naoko
A1 - Werner, Rudolf A.
A1 - Ueda, Yuichiro
A1 - Günther, Katharina
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Fukushima, Kazuhito
A1 - Edenhofer, Frank
A1 - Higuchi, Takahiro
T1 - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
T2 - International Journal of Cardiology
N2 - Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW - tracer
KW - Stammzelle
KW - induced pluripotent stem cells
KW - cardiomyocytes
KW - fatty acid
KW - stem cell therapy
KW - hiPSC-CM
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163320
SN - 0167-5273
ER -
TY - JOUR
A1 - Philipp-Abbrederis, Kathrin
A1 - Herrmann, Ken
A1 - Knop, Stefan
A1 - Schottelius, Margret
A1 - Eiber, Matthias
A1 - Lückerath, Katharina
A1 - Pietschmann, Elke
A1 - Habringer, Stefan
A1 - Gerngroß, Carlos
A1 - Franke, Katharina
A1 - Rudelius, Martina
A1 - Schirbel, Andreas
A1 - Lapa, Constantin
A1 - Schwamborn, Kristina
A1 - Steidle, Sabine
A1 - Hartmann, Elena
A1 - Rosenwald, Andreas
A1 - Kropf, Saskia
A1 - Beer, Ambros J
A1 - Peschel, Christian
A1 - Einsele, Hermann
A1 - Buck, Andreas K
A1 - Schwaiger, Markus
A1 - Götze, Katharina
A1 - Wester, Hans-Jürgen
A1 - Keller, Ulrich
T1 - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
JF - EMBO Molecular Medicine
N2 - 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.
KW - FDG PET/CT
KW - cells
KW - CXCR4/SDF-1
KW - CXCR4
KW - multiple myeloma
KW - positron emission tomography
KW - chemokine receptor
KW - in vivo imaging
KW - malignancies
KW - involvement
KW - microenvironment
KW - survival
KW - cancer
KW - autologous transplantation
KW - bone disease
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738
VL - 7
IS - 4
ER -
TY - JOUR
A1 - Rasche, Leo
A1 - Kumar, Manoj
A1 - Gershner, Grant
A1 - Samant, Rohan
A1 - Van Hemert, Rudy
A1 - Heidemeier, Anke
A1 - Lapa, Constantin
A1 - Bley, Thorsten
A1 - Buck, Andreas
A1 - McDonald, James
A1 - Hillengass, Jens
A1 - Epstein, Joshua
A1 - Thanendrarajan, Sharmilan
A1 - Schinke, Carolina
A1 - van Rhee, Frits
A1 - Zangari, Maurizio
A1 - Barlogie, Bart
A1 - Davies, Faith E.
A1 - Morgan, Gareth J.
A1 - Weinhold, Niels
T1 - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis?
JF - Theranostics
N2 - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM.
KW - multiple myeloma
KW - diffusion weighted mri
KW - spleen
KW - tumor burden
KW - high risk
KW - extramedullary hematopoiesis
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982
VL - 9
IS - 16
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 - Serfling, Sebastian E.
A1 - Lapa, Constantin
A1 - Dreher, Niklas
A1 - Hartrampf, Philipp E.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Schirbel, Andreas
A1 - Weich, Alexander
A1 - Hahner, Stefanie
A1 - Fassnacht, Martin
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
JF - Molecular Imaging and Biology
N2 - Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
KW - CXCR4
KW - C-X-C motif chemokine receptor 4
KW - PET
KW - [68Ga]PentixaFor
KW - [177Lu]/[90Y]PentixaTher
KW - theranostics
KW - endoradiotherapy
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622
VL - 24
IS - 4
ER -
TY - JOUR
A1 - Steinhardt, Maximilian Johannes
A1 - Zhou, Xiang
A1 - Krummenast, Franziska
A1 - Meckel, Katharina
A1 - Nickel, Katharina
A1 - Böckle, David
A1 - Messerschmidt, Janin
A1 - Knorz, Sebastian
A1 - Dierks, Alexander
A1 - Heidemeier, Anke
A1 - Lapa, Constantin
A1 - Einsele, Hermann
A1 - Rasche, Leo
A1 - Kortüm, Klaus Martin
T1 - Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma
JF - International Journal of Immunopathology and Pharmacology
N2 - We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab (“Pom-PAD-Dara”), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.
KW - CD38
KW - MOR202
KW - daratumumab
KW - multiple myeloma
KW - refractory
KW - relapse
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236235
VL - 34
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 - Tutov, Anna
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Mühlig, Saskia
A1 - Zimmermann, Thomas
A1 - Nose, Naoko
A1 - Koshino, Kazuhiro
A1 - Lapa, Constantin
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Rationalizing the binding modes of PET radiotracers targeting the norepinephrine transporter
JF - Pharmaceutics
N2 - Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure–activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer–NET interaction, whereby a T-shaped π–π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.
KW - positron emission tomography
KW - norepinephrine transporter
KW - sympathetic nervous system
KW - structure–activity relationships
KW - T-shaped π–π stacking
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303949
SN - 1999-4923
VL - 15
IS - 2
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Higuchi, Takahiro
A1 - Bundschuh, Ralph A.
A1 - Lapa, Constantin
A1 - Serfling, Sebastian E.
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Herrmann, Ken
A1 - Buck, Andreas K.
A1 - Derlin, Thorsten
A1 - Werner, Rudolf A.
T1 - Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers
JF - Molecular Imaging and Biology
N2 - Purpose
For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine.
Procedures
A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80).
Results
Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21).
Conclusions
A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.
KW - PET/CT
KW - neuroendocrine tumor
KW - PRRT
KW - peptide receptor radionuclide therapy
KW - reporting and data system
KW - SSTR-RADS
KW - RADS
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324645
VL - 24
IS - 4
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 - 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 - Werner, Rudolf A.
A1 - Beykan, Seval
A1 - Higuchi, Takahiro
A1 - Lückerath, Katharina
A1 - Weich, Alexander
A1 - Scheurlen, Michael
A1 - Bluemel, Christina
A1 - Herrmann, Ken
A1 - Buck, Andreas K.
A1 - Lassmann, Michael
A1 - Lapa, Constantin
A1 - Hänscheid, Heribert
T1 - The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy
JF - Oncotarget
N2 - 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.
KW - renal scintigraphy
KW - neuroendocrine tumor
KW - 177Lu
KW - MAG3
KW - PRRT
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177318
VL - 7
IS - 27
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Bundschuh, Lena
A1 - Fanti, Stefano
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Weich, A.
A1 - Pienta, Kenneth J.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Herrmann, Ken
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - Novel Structured Reporting Systems for Theranostic Radiotracers
T2 - Journal of Nuclear Medicine
N2 - Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.
KW - standardized reporting
KW - Positronen-Emissions-Tomografie
KW - prostate cancer
KW - neuroendocrine neoplasia
KW - 68Ga-DOTATATE
KW - 68Ga-DOTATOC
KW - 68Ga-DOTANOC
KW - somatostatin receptor
KW - SSTR
KW - prostate-specific membrane antigen
KW - PSMA
KW - RADS
KW - PSMA-RADS
KW - SSTR-RADS
KW - MI-RADS
KW - PROMISE
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174629
SN - 0161-5505
N1 - This research was originally published in JNM. Authors: Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Stefano Fanti, Mehrbod S. Javadi, Takahiro Higuchi, A. Weich, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Ken Herrmann, Constantin Lapa, Steven P. Rowe. Novel Structured Reporting Systems for Theranostic Radiotracers. J Nucl Med May 1, 2019 vol. 60 no. 5 577-584 © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Bundschuh, Lena
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Weich, Alexander
A1 - Sheikhbahaei, Sara
A1 - Pienta, Kenneth J.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications
JF - Annals of Nuclear Medicine
N2 - Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
KW - PET
KW - Positronen-Emissions-Tomografie
KW - prostate cancer
KW - neuroendocrine tumor
KW - prostate-specific membrane antigen (PSMA)
KW - somatostatin receptor (SSTR)
KW - positron emission tomography
KW - theranostics
KW - standardization
KW - RADS
KW - reporting and data systems
KW - personalized medicine
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166995
SN - 0914-7187
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Bundschuh, Lena
A1 - Javadi, Mehrbod S.
A1 - Leal, Jeffrey P.
A1 - Higuchi, Takahiro
A1 - Pienta, Kenneth J.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging
T2 - Journal of Nuclear Medicine
N2 - Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center.
Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed.
Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005).
Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
KW - 18F-DCFPyL
KW - Positronen-Emissions-Tomografie
KW - PSMA-RADS
KW - interreader
KW - interobserver
KW - PSMA
KW - prostate cancer
KW - RADS
KW - reporting and data system
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167788
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Mehrbod S. Javadi, Jeffrey P. Leal, Takahiro Higuchi, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Constantin Lapa and Steven P. Rowe. Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging. J Nucl Med 2018;59:1857-1864 © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Higuchi, Takahiro
A1 - Javadi, Mehrbod S.
A1 - Rowe, Steven P.
A1 - Zsótér, Norbert
A1 - Kroiss, Matthias
A1 - Fassnacht, Martin
A1 - Buck, Andreas K.
A1 - Kreissl, Michael C.
A1 - Lapa, Constantin
T1 - Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib
JF - Endocrine
N2 - Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
KW - personalized medicine
KW - Positronen-Emissions-Tomografie
KW - medullary thyroid carcinoma
KW - tyrosine kinase inhibitor
KW - TKI
KW - vandetanib
KW - 18F-FDG
KW - positron emission tomography
KW - 2-deoxy-2-(18F)fluoro-D-glucose
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167910
SN - 1355-008X
ER -
TY - CHAP
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Nose, Naoko
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
T1 - The Impact of Ageing on [\(^{11}\)C]meta-Hydroxyephedrine Uptake in the Rat Heart
T2 - Journal of Nuclear Medicine
N2 - No abstract available.
KW - Positronen-Emissions-Tomografie
KW - moycardial sympathetic innervation
KW - Positronen-Emissions-Tomografie
KW - positron emission tomography
KW - PET
KW - 11C-HED
KW - hydroxyephedrine
KW - ageing
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162228
UR - http://jnm.snmjournals.org/content/59/supplement_1/100.abstract
SN - 0161-5505
VL - 59
IS - Supplement No 1
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
T1 - SPECT vs. PET in Cardiac Innervation Imaging: Clash of the Titans
JF - Clinical and Translational Imaging
N2 - Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers.
Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.
KW - single photon emission computed tomography: sympathetic nerve
KW - Positronen-Emissions-Tomografie
KW - 18F-LMI1195
KW - 11C-hydroxyephedrine
KW - 123I-metaiodobenzylguanidine
KW - positron emission tomography
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163628
SN - 2281-5872
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Maya, Yoshifumi
A1 - Eissler, Christoph
A1 - Hirano, Mitsuru
A1 - Nose, Naoko
A1 - Wakabayashi, Hiroshi
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
T1 - The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart
JF - Scientific Reports
N2 - We aimed to explore the impact of ageing on 11C-Hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (−)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2–141.9 GBq/μmol) were prepared. \(^{11}\)C-HED (48.7±9.7MBq, ranged 0.2–60.4μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11CHED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.
KW - ageing
KW - Positronen-Emissions-Tomografie
KW - 11C-HED
KW - 11C-Hydroxyephedrine
KW - cardiac sympathetic nervous system
KW - myocardial sympathetic innervation imaging
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164826
SN - 2281-5872
VL - 8
IS - 11120
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
T1 - Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers
JF - The International Journal of Cardiovascular Imaging
N2 - The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.
KW - heart failure with mid-range ejection fraction
KW - Positronenemissionstomografie
KW - coronary artery disease
KW - precision medicine
KW - positron emission tomography
KW - PET
KW - SPECT
KW - myocardial perfusion imaging
KW - MPI
KW - 18F-flurpiridaz
KW - 18FFBnTP
KW - HFmrEF
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169134
SN - 1569-5794
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 - Werner, Rudolf A.
A1 - Eissler, Christoph
A1 - Hayakawa, Nobuyuki
A1 - Arias-Loza, Paula
A1 - Wakabayashi, Hiroshi
A1 - Javadi, Mehrbod S.
A1 - Chen, Xinyu
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Pelzer, Theo
A1 - Higuchi, Takahiro
T1 - Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
JF - Scientific Reports
N2 - In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
KW - diabetic cardiomyopathy
KW - personalized treatment
KW - precision medicine
KW - ZDF rats
KW - ECG
KW - PET
KW - \(^{18}\)F-fluorodeoxyglucose
KW - \(^{18}\)F-FDG
KW - diabetes
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171765
VL - 8
IS - 17631
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Habacha, Bilêl
A1 - Lütje, Susanne
A1 - Bundschuh, Lena
A1 - Higuchi, Takahiro
A1 - Hartrampf, Philipp
A1 - Serfling, Sebastian E.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Essler, Markus
A1 - Pienta, Kenneth J.
A1 - Eisenberger, Mario A.
A1 - Markowski, Mark C.
A1 - Shinehouse, Laura
A1 - AbdAllah, Rehab
A1 - Salavati, Ali
A1 - Lodge, Martin A.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Bundschuh, Ralph A.
A1 - Rowe, Steven P.
T1 - High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL
JF - Molecular Imaging
N2 - No abstract available.
KW - SUV
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300748
VL - 2022
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Ilhan, Harun
A1 - Lehner, Sebastian
A1 - Papp, László
A1 - Zsótér, Norbert
A1 - Schatka, Imke
A1 - Muegge, Dirk O.
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Bartenstein, Peter
A1 - Bengel, Frank
A1 - Essler, Markus
A1 - Lapa, Constantin
A1 - Bundschuh, Ralph A.
T1 - Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy
T2 - Molecular Imaging and Biology
N2 - Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
KW - Pancreas
KW - Positronen-Emissions-Tomografie
KW - PET
KW - neuroendocrine tumor
KW - tumor heterogeneity
KW - [68Ga]
KW - [177Lu]-DOTATATE/-DOTATOC
KW - PET/CT
KW - SSTR
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164624
UR - https://link.springer.com/article/10.1007/s11307-018-1252-5
SN - 1536-1632
N1 - This is a post-peer-review, pre-copyedit version of an article published in Molecular Imaging and Biology. The final authenticated version is available online at: http://dx.doi.org/s11307-018-1252-5
N1 - Die finale Version dieses Artikels steht unter https://doi.org/10.1007/s11307-018-1252-5 bzw. http://nbn-resolving.org/urn:nbn:de:bvb:20-opus-167168 open access zur Verfügung.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Ilhan, Harun
A1 - Lehner, Sebastian
A1 - Papp, László
A1 - Zsótér, Norbert
A1 - Schatka, Imke
A1 - Muegge, Dirk O.
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Bartenstein, Peter
A1 - Bengel, Frank
A1 - Essler, Markus
A1 - Lapa, Constantin
A1 - Bundschuh, Ralph A.
T1 - Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy
JF - Molecular Imaging and Biology
N2 - Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
KW - tumor heterogeneity
KW - Positronen-Emissions-Tomografie
KW - PET
KW - PET/CT
KW - pancreas
KW - SSTR
KW - [177Lu]-DOTATATE/-DOTATOC
KW - [68Ga]
KW - neuroendocrine tumor
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167168
SN - 1536-1632
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 - Werner, Rudolf A.
A1 - Kobayashi, Ryohei
A1 - Javadi, Mehrbod Som
A1 - Köck, Zoe
A1 - Wakabayashi, Hiroshi
A1 - Unterecker, Stefan
A1 - Nakajima, Kenichi
A1 - Lapa, Constantin
A1 - Menke, Andreas
A1 - Higuchi, Takahiro
T1 - Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits
JF - Journal of Nuclear Medicine
N2 - Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results.
Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 % for desipramine, 25.5 % for venlafaxine, 11.7 % for bupropion and 0.72 % for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake.
Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.
KW - MDD
KW - Antidepressants
KW - depression
KW - 123I-mIBG
KW - antidepressant
KW - cardiac sympathetic nerve system
KW - major depressive disorder
KW - myocardial sympathetic innervation imaging
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161280
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi. Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1099-1103. © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Lapa, Constantin
A1 - Bluemel, Christina
A1 - Lückerath, Katharina
A1 - Schirbel, Andreas
A1 - Strate, Alexander
A1 - Buck, Andreas K.
A1 - Herrmann, Ken
T1 - Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy
N2 - 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.
KW - NET
KW - PRRT
KW - Hyperkalaemia
KW - Arginine
KW - Lysine
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110617
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 - 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 - The Impact of Ageing on Dopamine Transporter Imaging
T2 - Journal of Nuclear Medicine
N2 - No abstract available.
KW - Parkinson-Krankheit
KW - Parkinson
KW - Parkinson Disease
KW - DaTscan
KW - Ioflupane
KW - SPECT
KW - molecular imaging
KW - ageing
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162213
UR - http://jnm.snmjournals.org/content/59/supplement_1/1646.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. The Impact of Ageing on Dopamine Transporter Imaging. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:1646. © SNMMI.
VL - 59
IS - Supplement No 1
SP - 1646
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Marcus, Charles
A1 - Sheikhbahaei, Sara
A1 - Solnes, Lilja B.
A1 - Leal, Jeffrey P.
A1 - Du, Yong
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
T1 - Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging
JF - Clinical Nuclear Medicine
N2 - PURPOSE:
We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists.
METHODS:
An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software.
RESULTS:
When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found.
CONCLUSIONS:
In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.
KW - Single-Photon-Emissions-Computertomographie
KW - SPECT
KW - Parkinson’s disease
KW - Parkinsonism
KW - DaTscan
KW - 123I-Ioflupane
KW - SPECT
KW - SPECT/CT
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168181
SN - 1536-0229
VL - 44
IS - 1
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Ordonez, Alvaro A.
A1 - Sanchez-Bautista, Julian
A1 - Marcus, Charles
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Leal, Jeffrey P.
A1 - Lodge, Martin A.
A1 - Javadi, Mehrbod S.
A1 - Jain, Sanjay K.
A1 - Higuchi, Takahiro
T1 - Novel functional renal PET imaging with 18F-FDS in human subjects
JF - Clinical Nuclear Medicine
N2 - The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure.
KW - 2-deoxy-2-18F-fluoro-D-sorbitol
KW - Positronen-Emissions-Tomografie
KW - 18F-FDS
KW - renal imaging
KW - Positron-Emission Tomography
KW - split renal function
KW - kidney
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174634
SN - 0363-9762
VL - 44
IS - 5
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Sheikhbahaei, Sara
A1 - Jones, Krystyna M.
A1 - Javadi, Mehrbod S.
A1 - Solnes, Lilja B.
A1 - Ross, Ashley E.
A1 - Allaf, Mohamad E.
A1 - Pienta, Kenneth J.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Gorin, Micheal A.
A1 - Rowe, Steven P.
T1 - Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia
JF - Annals of Nuclear Medicine
N2 - Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL.
Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean).
Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.
Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.
KW - 18F-DCFPL
KW - Positronen-Emissions-Tomografie
KW - Prostata
KW - PSMA
KW - Ganglia
KW - Pitfall
KW - PET
KW - Tracer
KW - Radiotracer
KW - Imaging pitfalls
KW - Prostate Cancer
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166971
SN - 0914-7187
VL - 31
IS - 9
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Wakabayashi, Hiroshi
A1 - Chen, Xinyu
A1 - Hayakawa, Nobuyuki
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
A1 - Javadi, Mehrbod S.
A1 - Robinson, Simon
A1 - Higuchi, Takahiro
T1 - Ventricular distribution pattern of the novel sympathetic nerve PET radiotracer \(^{18}\)F-LMI1195 in Rabbit Hearts
JF - Scientific Reports
N2 - We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer \(^{18}\)F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of \(^{18}\)F-LMI1195. In healthy rabbits, \(^{18}\)F-LMI1195 was administered followed by the reference perfusion marker \(^{201}\)Tl for a dual-radiotracer analysis. After 20 min of \(^{18}\)F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-μm short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine \(^{18}\)F-LMI1195 distribution (exposure for 3 h). After complete \(^{18}\)F decay, sections were re-exposed to determine 201Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. \(^{18}\)F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 ± 2, 94 ± 5, 94 ± 4 and 97 ± 3%LV, respectively, n.s.). Subepicardial \(^{201}\)Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90 ± 3, 96 ± 2 and *80 ± 5%LV, respectively, *p < 0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of \(^{18}\)F-LMI1195 (90 ± 4, 96 ± 5 and 84 ± 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of \(^{201}\)Tl in comparison to \(^{18}\)F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts.
KW - Cardiovascular diseases
KW - Heart failure
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202707
VL - 9
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Weich, Alexander
A1 - Higuchi, Takahiro
A1 - Schmid, Jan S.
A1 - Schirbel, Andreas
A1 - Lassmann, Michael
A1 - Wild, Vanessa
A1 - Rudelius, Martina
A1 - Kudlich, Theodor
A1 - Herrmann, Ken
A1 - Scheurlen, Michael
A1 - Buck, Andreas K.
A1 - Kropf, Saskia
A1 - Wester, Hans-Jürgen
A1 - Lapa, Constantin
T1 - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF - Theranostics
N2 - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW - SSTR
KW - peptide receptor radionuclide therapy
KW - neuroendocrine tumor
KW - [\(^{68}\)Ga]Pentixafor
KW - CXCR4
KW - chemokine receptor
KW - PET/CT
KW - DOTATOC
KW - PRRT
KW - Positronen-Emissions-Tomografie
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL - 7
IS - 6
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Weich, Alexander
A1 - Kircher, Malte
A1 - Solnes, Lilja B.
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven
A1 - Lapa, Constantin
T1 - The theranostic promise for neuroendocrine tumors in the late 2010s – Where do we stand, where do we go?
JF - Theranostics
N2 - More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.
KW - theranostics
KW - Positronen-Emissions-Tomografie
KW - PRRT
KW - somatostatin receptor
KW - peptide receptor radionuclide therapy
KW - neuroendocrine tumor
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170264
VL - 8
IS - 22
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Chen, Xinyu
A1 - Lapa, Constantin
A1 - Robinson, Simon
A1 - Higuchi, Takahiro
T1 - Intracellular behavior of the novel sympathetic nerve agent \(^{18}\)F-LMI1195
T2 - Journal of Nuclear Cardiology
N2 - No abstract available.
KW - Herz
KW - PET
KW - sympathetic nerve
KW - autonomic nervous system
KW - 18F-LMI1195
KW - positron emission tomography
KW - heart
KW - cardiac
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161137
SN - 1071-3581
N1 - This is a post-peer-review, pre-copyedit version of an article published in J Nucl Cardiol. ISSN: 1071-3581. Supplement (2017) Aug;24;4: 1461-1496. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12350-017-0984-y
VL - 24
IS - 4 Supplement (2017) Aug
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 - CHAP
A1 - Werner, Rudolf
A1 - Higuchi, Takahiro
A1 - Muegge, Dirk
A1 - Javadi, Mehrbod S.
A1 - Märkl, Bruno
A1 - Aulmann, Christoph
A1 - Buck, Andreas K.
A1 - Fassnacht, Martin
A1 - Lapa, Constantin
A1 - Kreissl, Michael C.
T1 - Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment
T2 - Journal of Nuclear Medicine
N2 - Introduction: The prognosis of medullary thyroid carcinoma (MTC) is poor using common chemotherapeutic approaches. However, during the last years encouraging results of recently introduced tyrosine kinase inhibitors (TKI) such as vandetanib have been published. In this study we aimed to correlate the results of \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG) positron emission tomography (PET) imaging with treatment outcome.
Methods: Eighteen patients after thyroidectomy with recurrent/advanced MTC lesions receiving vandetanib (300 mg orally/day) could be analysed. A baseline \(^{18}\)F-FDG PET prior to and a follow-up \(^{18}\)F-FDG PET 3 months after TKI initiation were performed. During follow-up, tumor progression was assessed every 3 months including computed tomography according to RECIST. Progression-free survival (PFS) was correlated with the maximum standardized uptake value of \(^{18}\)F-FDG in lymph nodes (SUV(LN)max) or visceral metastases (SUV(MTS)max) as well as with clinical parameters using ROC analysis.
Results: Within median 3.6 years of follow-up, 9 patients showed disease progression at median 8.5 months after TKI initiation. An elevated glucose consumption assessed by baseline \(^{18}\)F-FDG PET (SUV(LN)max > 7.25) could predict a shorter PFS (2 y) with an accuracy of 76.5% (SUV(LN)max <7.25, 4.3 y; p=0.03). Accordingly, preserved tumor metabolism in the follow-up PET (SUV(MTS)max >2.7) also demonstrated an unfavorable prognosis (accuracy, 85.7%). On the other hand, none of the clinical parameters reached significance in response prediction.
Conclusions: In patients with advanced and progressive MTC, tumors with higher metabolic activity at baseline are more aggressive and more prone to progression as reflected by a shorter PFS; they should be monitored more closely. Preserved glucose consumption 3 months after treatment initiation was also related to poorer prognosis.
KW - 18F-FDG
KW - vandetanib
KW - TKI
KW - PET
KW - positron emission tomography
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161147
UR - http://jnm.snmjournals.org/content/58/supplement_1/169
SN - 0161-5505
N1 - This research was originally published in JNM.
Rudolf A. Werner, Takahiro Higuchi, Dirk O. Muegge, Mehrbod S. Javadi, B. Märkl, C. Aulmann, Andreas K. Buck, Martin Fassnacht, Constantin Lapa, Michael C. Kreissl.
Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment. J Nucl Med. May 1, 2017; vol. 58 no. supplement 1:169. © SNMMI.
VL - 58
IS - no. supplement 1
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Hänscheid, Heribert
A1 - Leal, Jeffrey P.
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Lodge, Martin A.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution
JF - Molecular Imaging and Biology
N2 - Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.
Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden.
Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET.
Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.
KW - somatostatin receptor
KW - Positronen-Emissions-Tomografie
KW - quantification
KW - [68Ga]DOTATOC
KW - neuroendocrine tumor
KW - SSTR-PET
KW - theranostics
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170280
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 - CHAP
A1 - Werner, Rudolf
A1 - Lapa, Constantin
A1 - Buck, Andreas
A1 - Lassmann, Michael
A1 - Hänscheid, Heribert
T1 - Less is sometimes more – Accurate Dose Mapping after Endoradiotherapy with \(^{177}\)Lu-DOTATATE/-TOC by One-Single Measurement after 96 h
T2 - Journal of Nuclear Medicine
N2 - No abstract available.
KW - Neuroendocrine Tumor
KW - theranostics
KW - 177Lu-DOTATATE
KW - 177Lu-DOTATOC
KW - PRRT
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161168
UR - http://jnm.snmjournals.org/content/58/supplement_1/247.abstract
SN - 0161-5505
N1 - This research was originally published in JNM. Werner R.A., Lapa C., Buck A.K., Lassmann M., Hänscheid H.Less is sometimes more – Accurate Dose Mapping after Endoradiotherapy with 177Lu-DOTATATE/-TOC by One-Single Measurement after 96 h. J Nucl Med May 1, 2017 vol. 58 no. supplement 1:247. © SNMMI
VL - 58
IS - No. Supplement 1
PB - Society of Nuclear Medicine and Molecular Imaging
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Schmid, Jan-Stefan
A1 - Higuchi, Takahiro
A1 - Javadi, Mehrbod S.
A1 - Rowe, Steven P.
A1 - Märkl, Bruno
A1 - Aulmann, Christoph
A1 - Fassnacht, Martin
A1 - Kroiß, Matthias
A1 - Reiners, Christoph
A1 - Buck, Andreas
A1 - Kreissl, Michael
A1 - Lapa, Constantin
T1 - Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib
JF - Journal of Nuclear Medicine
N2 - Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We
aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment.
Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type).
Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation.
Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance.
Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
KW - positron emission tomography
KW - Medullärer Schilddrüsenkrebs
KW - Positronen-Emissions-Tomografie
KW - medullary thyroid carcinoma
KW - tyrosine kinase inhibitor
KW - vandetanib
KW - 2- deoxy-2-(18F)fluoro-D-glucose
KW - 18F-FDG
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161256
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Jan-Stefan Schmid, Takahiro Higuchi, Mehrbod S. Javadi, Steven P. Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K. Buck, Michael C. Kreissl, Constantin Lapa. Predictive value of 18F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. May 1, 2018;vol. 59 no. 5: 756-761. © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Solnes, Lilja
A1 - Javadi, Mehrbod
A1 - Weich, Alexander
A1 - Gorin, Michael
A1 - Pienta, Kenneth
A1 - Higuchi, Takahiro
A1 - Buck, Andreas
A1 - Pomper, Martin
A1 - Rowe, Steven
A1 - Lapa, Constantin
T1 - SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework
JF - Journal of Nuclear Medicine
N2 - Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.
KW - Radionuclide Therapy
KW - Standardisierung
KW - Positronen-Emissions-Tomografie
KW - 68Ga-DOTATATE/-TOC
KW - Gastrointestinal
KW - Neuroendocrine
KW - Neuroendocrine Tumor
KW - Oncology
KW - GI
KW - PET
KW - PET/CT
KW - PRRT
KW - RADS
KW - SSTR
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161298
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Lilja B. Solnes, Mehrbod Som Javadi, Alexander Weich, Michael A. Gorin, Kenneth J. Pienta, Takahiro Higuchi, Andreas K. Buck, Martin G. Pomper, Steven P. Rowe, Constantin Lapa. SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1085-1091. © SNMMI
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Wakabayashi, Hiroshi
A1 - Bauer, Jochen
A1 - Schütz, Claudia
A1 - Zechmeister, Christina
A1 - Hayakawa, Nobuyuki
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Jahns, Roland
A1 - Ergün, Süleyman
A1 - Jahns, Valerie
A1 - Higuchi, Takahiro
T1 - Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
JF - European Heart Journal Cardiovascular Imaging
N2 - Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.
Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).
Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
KW - positron emission tomography
KW - Myokarditis
KW - myocarditis
KW - inflammation
KW - 18F-FDG
KW - PET
KW - personalized treatment
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165601
SN - 2047-2404
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Wakabyashi, Hiroshi
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Rowe, Steven
A1 - Javadi, Mehrbod
A1 - Higuchi, Takahiro
T1 - Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders
JF - Journal of Nuclear Medicine
N2 - Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases.
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05).
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
KW - unilateral ureteral obstruction
KW - Nierenfunktionsstörung
KW - Positronen-Emissions-Tomografie
KW - 18F-FDS
KW - 99mTc-DTPA
KW - PET
KW - renal failure
KW - Glomerular filtration
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161279
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P. Rowe, Mehrbod S. Javadi and Takahiro Higuchi. Functional renal imaging with 18F-FDS PET in rat models of renal disorders. J Nucl Med. May 1, 2018;vol. 59 no. 5: 828-832. © SNMMI.
ER -
TY - INPR
A1 - Yin, Yafu
A1 - Werner, Rudolf A.
A1 - Higuchi, Takahiro
A1 - Lapa, Constantin
A1 - Pienta, Kenneth J.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
T1 - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories
T2 - Journal of Nuclear Medicine
N2 - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa.
Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy.
Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up.
Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
KW - PSMA-RADS-3B
KW - Positronen-Emissions-Tomografie
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - PSMA-targeted PET
KW - PSMA-RADS-3A
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167594
SN - 0161-5505
N1 - This research was originally published in JNM. Yafu Yin, Rudolf A. Werner, Takahiro Higuchi, Constantin Lapa, Kenneth J. Pienta, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe.
Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA-RADS-3B Categories. J Nucl Med. 2019;60:511-516 © SNMMI.
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 - Zhou, Xiang
A1 - Dierks, Alexander
A1 - Kertels, Olivia
A1 - Samnick, Samuel
A1 - Kircher, Malte
A1 - Buck, Andreas K.
A1 - Haertle, Larissa
A1 - Knorz, Sebastian
A1 - Böckle, David
A1 - Scheller, Lukas
A1 - Messerschmidt, Janin
A1 - Barakat, Mohammad
A1 - Truger, Marietta
A1 - Haferlach, Claudia
A1 - Einsele, Hermann
A1 - Rasche, Leo
A1 - Kortüm, K. Martin
A1 - Lapa, Constantin
T1 - The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT
JF - Cancers
N2 - Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.
KW - radiogenomics
KW - 18F-FDG PET/CT
KW - multiple myeloma
KW - relapse
KW - progression
KW - pattern
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211157
SN - 2072-6694
VL - 12
IS - 9
ER -