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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 -