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  - 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  - 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  - 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  - 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  - 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  - 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  - CHAP
A1  - Werner, Rudolf A.
A1  - Marcus, Charles
A1  - Sheikhbahaei, Sara
A1  - Higuchi, Takahiro
A1  - Solnes, Lilja B.
A1  - Rowe, Steven P.
A1  - Buck, Andreas K.
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
T1  - Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method
T2  - Journal of Nuclear Medicine
N2  - No abstract available.
KW  - Parkinson-Krankheit
KW  - SPECT
KW  - Parkinson
KW  - Parkinson Disease
KW  - DaTscan
KW  - Ioflupane
KW  - molecular imaging
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162208
UR  - http://jnm.snmjournals.org/content/59/supplement_1/626.abstract
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI.
VL  - 59
IS  - Supplement No. 1
SP  - 626
ER  - 
TY  - JOUR
A1  - 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  -