@article{WeichHiguchiBundschuhetal.2022,
  author    = {Weich, Alexander and Higuchi, Takahiro and Bundschuh, Ralph A. and Lapa, Constantin and Serfling, Sebastian E. and Rowe, Steven P. and Pomper, Martin G. and Herrmann, Ken and Buck, Andreas K. and Derlin, Thorsten and Werner, Rudolf A.},
  title     = {Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers},
  series = {Molecular Imaging and Biology},
  volume    = {24},
  journal   = {Molecular Imaging and Biology},
  number    = {4},
  doi       = {10.1007/s11307-022-01712-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324645},
  pages     = {631-640},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{HartrampfWeinzierlSerflingetal.2022,
  author    = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Serfling, Sebastian E. and Pomper, Martin G. and Rowe, Steven P. and Higuchi, Takahiro and Seitz, Anna Katharina and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A.},
  title     = {Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I\&T},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {3},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14030647},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254825},
  year      = {2022},
  abstract  = {(1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [\(^{177}\)Lu]Lu-PSMA I\&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [\(^{177}\)Lu]Lu-PSMA I\&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [\(^{99m}\)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22\%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67\%) according to eGFR. Only 5/42 (13\%) showed reduced TER, defined as <70\% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2\% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1\%; GFR, 1/49 (2\%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2\%); G3a to G3b, 2/49 (4.1\%)). After three cycles, follow-up eGFR correlated negatively with age (r = -0.40, p = 0.005) and the eGFR change with Gleason score (r = -0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2\%) (CTCAE I, 20/49 (41\%)) and CTCAE I thrombocytopenia in 7/49 (14\%), with an absolute decrease of 15.2\% and 16.6\% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20\%) (CTCAE I, 36/49 (73\%)) with a decrease in hemoglobin of 4.7\%. (4) Conclusions: After PSMA-targeted therapy using [\(^{177}\)Lu]Lu-PSMA I\&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.},
  language  = {en}
}
@article{GargWernerChungetal.2022,
  author    = {Garg, Tushar and Werner, Rudolf A. and Chung, Hyun Woo and Khatri, Wajahat and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Saad, Elie and Rowe, Steven P.},
  title     = {Association of true positivity with serum prostate-specific antigen levels and other clinical factors in indeterminate PSMA-RADS-3A lesions identified on \(^{18}\)F-DCFPyL PET/CT scans},
  series = {Tomography},
  volume    = {8},
  journal   = {Tomography},
  number    = {6},
  issn      = {2379-139X},
  doi       = {10.3390/tomography8060220},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290510},
  pages     = {2639 -- 2647},
  year      = {2022},
  abstract  = {The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on \(^{18}\)F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0-0.2, 0.2-1, 1-2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59-81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2\% vs. 81.9\%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12\% (95\% CI = 73.69-86.16\%), and the area under the curve was 71.32\% (95\% CI = 61.9-80.7\%, p < 0.0001). A total of 96.4\% (108/112) of patients with positive lesions and 86.4\% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial \(^{18}\)F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.},
  language  = {en}
}
@article{WernerHabachaLuetjeetal.2022,
  author    = {Werner, Rudolf A. and Habacha, Bil{\^e}l and L{\"u}tje, Susanne and Bundschuh, Lena and Higuchi, Takahiro and Hartrampf, Philipp and Serfling, Sebastian E. and Derlin, Thorsten and Lapa, Constantin and Buck, Andreas K. and Essler, Markus and Pienta, Kenneth J. and Eisenberger, Mario A. and Markowski, Mark C. and Shinehouse, Laura and AbdAllah, Rehab and Salavati, Ali and Lodge, Martin A. and Pomper, Martin G. and Gorin, Michael A. and Bundschuh, Ralph A. and Rowe, Steven P.},
  title     = {High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL},
  series = {Molecular Imaging},
  volume    = {2022},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2022/7056983},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300748},
  year      = {2022},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{MatsusakaChenAriasLozaetal.2022,
  author    = {Matsusaka, Yohji and Chen, Xinyu and Arias-Loza, Paula and Werner, Rudolf A. and Nose, Naoko and Sasaki, Takanori and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Higuchi, Takahiro},
  title     = {In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats},
  series = {Molecular Imaging},
  volume    = {2022},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2022/4635171},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300708},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{ChenWernerKoshinoetal.2022,
  author    = {Chen, Xinyu and Werner, Rudolf A. and Koshino, Kazuhiro and Nose, Naoko and M{\"u}hlig, Saskia and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Decker, Michael and Higuchi, Takahiro},
  title     = {Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78},
  series = {Theranostics},
  volume    = {12},
  journal   = {Theranostics},
  number    = {9},
  doi       = {10.7150/thno.63205},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300685},
  pages     = {4446 -- 4458},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{MihatschBeissertPomperetal.2022,
  author    = {Mihatsch, Patrick W. and Beissert, Matthias and Pomper, Martin G. and Bley, Thorsten A. and Seitz, Anna K. and K{\"u}bler, Hubert and Buck, Andreas K. and Rowe, Steven P. and Serfling, Sebastian E. and Hartrampf, Philipp E. and Werner, Rudolf A.},
  title     = {Changing threshold-based segmentation has no relevant impact on semi-quantification in the context of structured reporting for PSMA-PET/CT},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14020270},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254782},
  year      = {2022},
  abstract  = {Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50\%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50\% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.},
  language  = {en}
}