@article{NoseNogamiKoshinoetal.2021, author = {Nose, Naoko and Nogami, Suguru and Koshino, Kazuhiro and Chen, Xinyu and Werner, Rudolf A. and Kashima, Soki and Rowe, Steven P. and Lapa, Constantin and Fukuchi, Kazuki and Higuchi, Takahiro}, title = {[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-90383-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260590}, year = {2021}, abstract = {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.}, language = {en} } @article{WernerDerlinLapaetal.2020, author = {Werner, Rudolf A. and Derlin, Thorsten and Lapa, Constantin and Sheikbahaei, Sara and Higuchi, Takahiro and Giesel, Frederik L. and Behr, Spencer and Drzezga, Alexander and Kimura, Hiroyuki and Buck, Andreas K. and Bengel, Frank M. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.}, title = {\(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging}, series = {Theranostics}, volume = {10}, journal = {Theranostics}, number = {1}, issn = {1838-7640}, doi = {10.7150/thno.37894}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202559}, pages = {1-16}, year = {2020}, abstract = {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.}, language = {en} } @unpublished{WernerAndreeJavadietal.2018, author = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.}, title = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging}, series = {Urology - The Gold Journal}, journal = {Urology - The Gold Journal}, issn = {0090-4295}, doi = {10.1016/j.urology.2018.03.030}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161103}, year = {2018}, abstract = {No abstract available.}, subject = {Virchow Node}, language = {en} } @article{WernerAndreeJavadietal.2018, author = {Werner, Rudolf A. and Andree, Christian and Javadi, Mehrbod S. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P. and Pienta, Kenneth J.}, title = {A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging}, series = {Urology - The Gold Journal}, volume = {117}, journal = {Urology - The Gold Journal}, issn = {0090-4295}, doi = {10.1016/j.urology.2018.03.030}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164632}, pages = {18-21}, year = {2018}, abstract = {No abstract available.}, language = {en} } @article{KosmalaSerflingDreheretal.2022, author = {Kosmala, Aleksander and Serfling, Sebastian E. and Dreher, Niklas and Lindner, Thomas and Schirbel, Andreas and Lapa, Constantin and Higuchi, Takahiro and Buck, Andreas K. and Weich, Alexander and Werner, Rudolf A.}, title = {Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {11}, issn = {2072-6694}, doi = {10.3390/cancers14112609}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275154}, year = {2022}, abstract = {(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.}, language = {en} } @article{JanssenHoffmannKannoetal.2020, author = {Janssen, Jan P. and Hoffmann, Jan V. and Kanno, Takayuki and Nose, Naoko and Grunz, Jan-Peter and Onoguchi, Masahisa and Chen, Xinyu and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro}, title = {Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-75696-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230616}, year = {2020}, abstract = {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.}, language = {en} } @article{ToyamaWernerRuizBedoyaetal.2021, author = {Toyama, Yoshitaka and Werner, Rudolf A. and Ruiz-Bedoya, Camilo A. and Ordonez, Alvaro A. and Takase, Kei and Lapa, Constantin and Jain, Sanjay K. and Pomper, Martin G. and Rowe, Steven P. and Higuchi, Takahiro}, title = {Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon}, series = {Theranostics}, volume = {11}, journal = {Theranostics}, number = {12}, doi = {10.7150/thno.58682}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260090}, pages = {6105-6119}, year = {2021}, abstract = {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.}, language = {en} } @article{WernerKircherHiguchietal.2019, author = {Werner, Rudolf A. and Kircher, Stefan and Higuchi, Takahiro and Kircher, Malte and Schirbel, Andreas and Wester, Hans-J{\"u}rgen and Buck, Andreas K. and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin}, title = {CXCR4-directed imaging in solid tumors}, series = {Frontiers in Oncology}, volume = {9}, journal = {Frontiers in Oncology}, number = {770}, issn = {2234-943X}, doi = {10.3389/fonc.2019.00770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195678}, year = {2019}, abstract = {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-na{\"i}ve 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-na{\"i}ve 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.}, language = {en} } @article{WeichWernerBucketal.2021, author = {Weich, Alexander and Werner, Rudolf A. and Buck, Andreas K. and Hartrampf, Philipp E. and Serfling, Sebastian E. and Scheurlen, Michael and Wester, Hans-J{\"u}rgen and Meining, Alexander and Kircher, Stefan and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Kircher, Malte}, title = {CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas}, series = {Diagnostics}, volume = {11}, journal = {Diagnostics}, number = {4}, issn = {2075-4418}, doi = {10.3390/diagnostics11040605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234231}, year = {2021}, abstract = {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-na{\"i}ve 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.}, language = {en} } @article{LambertiniHartrampfHiguchietal.2022, author = {Lambertini, Alessandro and Hartrampf, Philipp E. and Higuchi, Takahiro and Serfling, Sebastian E. and Meybohm, Patrick and Schirbel, Andreas and Buck, Andreas K. and Werner, Rudolf A.}, title = {CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {50}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {1}, doi = {10.1007/s00259-022-05932-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324619}, pages = {228-229}, year = {2022}, abstract = {No abstract available.}, language = {en} } @inproceedings{WernerMarcusSheikhbahaeietal.2018, author = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Higuchi, Takahiro and Solnes, Lilja B. and Rowe, Steven P. and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.}, title = {Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method}, series = {Journal of Nuclear Medicine}, volume = {59}, booktitle = {Journal of Nuclear Medicine}, number = {Supplement No. 1}, issn = {0161-5505}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162208}, pages = {626}, year = {2018}, abstract = {No abstract available.}, subject = {Parkinson-Krankheit}, language = {en} } @inproceedings{WernerKobayashiWakabayashietal.2017, author = {Werner, Rudolf and Kobayashi, Ryohei and Wakabayashi, Hiroshi and Lapa, Constantin and Menke, Andreas and Higuchi, Takahiro}, title = {Effect of Antidepressants on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake}, series = {European Heart Journal - Cardiovascular Imaging}, volume = {18}, booktitle = {European Heart Journal - Cardiovascular Imaging}, number = {Supplement}, publisher = {Oxford University Press}, issn = {2047-2404}, doi = {10.1093/ehjci/jex080}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161116}, pages = {i52-53}, year = {2017}, abstract = {No abstract available.}, subject = {MIBG}, language = {en} } @unpublished{YinWernerHiguchietal.2018, author = {Yin, Yafu and Werner, Rudolf A. and Higuchi, Takahiro and Lapa, Constantin and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.}, title = {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}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.217653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167594}, year = {2018}, abstract = {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.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{WernerWakabyashiChenetal.2018, author = {Werner, Rudolf and Wakabyashi, Hiroshi and Chen, Xinyu and Hirano, Mitsuru and Shinaji, Tetsuya and Lapa, Constantin and Rowe, Steven and Javadi, Mehrbod and Higuchi, Takahiro}, title = {Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.117.203828}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161279}, year = {2018}, abstract = {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.}, subject = {Nierenfunktionsst{\"o}rung}, language = {en} } @article{WernerHiguchiNoseetal.2022, author = {Werner, Rudolf A. and Higuchi, Takahiro and Nose, Naoko and Toriumi, Fujio and Matsusaka, Yohji and Kuji, Ichiei and Kazuhiro, Koshino}, title = {Generative adversarial network-created brain SPECTs of cerebral ischemia are indistinguishable to scans from real patients}, series = {Scientific reports}, volume = {12}, journal = {Scientific reports}, doi = {10.1038/s41598-022-23325-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300757}, year = {2022}, abstract = {Deep convolutional generative adversarial networks (GAN) allow for creating images from existing databases. We applied a modified light-weight GAN (FastGAN) algorithm to cerebral blood flow SPECTs and aimed to evaluate whether this technology can generate created images close to real patients. Investigating three anatomical levels (cerebellum, CER; basal ganglia, BG; cortex, COR), 551 normal (248 CER, 174 BG, 129 COR) and 387 pathological brain SPECTs using N-isopropyl p-I-123-iodoamphetamine (123I-IMP) were included. For the latter scans, cerebral ischemic disease comprised 291 uni- (66 CER, 116 BG, 109 COR) and 96 bilateral defect patterns (44 BG, 52 COR). Our model was trained using a three-compartment anatomical input (dataset 'A'; including CER, BG, and COR), while for dataset 'B', only one anatomical region (COR) was included. Quantitative analyses provided mean counts (MC) and left/right (LR) hemisphere ratios, which were then compared to quantification from real images. For MC, 'B' was significantly different for normal and bilateral defect patterns (P < 0.0001, respectively), but not for unilateral ischemia (P = 0.77). Comparable results were recorded for LR, as normal and ischemia scans were significantly different relative to images acquired from real patients (P ≤ 0.01, respectively). Images provided by 'A', however, revealed comparable quantitative results when compared to real images, including normal (P = 0.8) and pathological scans (unilateral, P = 0.99; bilateral, P = 0.68) for MC. For LR, only uni- (P = 0.03), but not normal or bilateral defect scans (P ≥ 0.08) reached significance relative to images of real patients. With a minimum of only three anatomical compartments serving as stimuli, created cerebral SPECTs are indistinguishable to images from real patients. The applied FastGAN algorithm may allow to provide sufficient scan numbers in various clinical scenarios, e.g., for "data-hungry" deep learning technologies or in the context of orphan diseases.}, language = {en} } @article{KazuhinoWernerToriumietal.2018, author = {Kazuhino, Koshino and Werner, Rudolf A. and Toriumi, Fuijo and Javadi, Mehrbod S. and Pomper, Martin G. and Solnes, Lilja B. and Verde, Franco and Higuchi, Takahiro and Rowe, Steven P.}, title = {Generative Adversarial Networks for the Creation of Realistic Artificial Brain Magnetic Resonance Images}, series = {Tomography}, volume = {4}, journal = {Tomography}, number = {4}, doi = {10.18383/j.tom.2018.00042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172185}, pages = {159-163}, year = {2018}, abstract = {Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)-based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40\%-60\%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45\% and 71\% as real magnetic resonance imaging images (NNRs, 24\%, 40\%, and 44\%). In contradistinction, 44\% and 70\% of the real images were rated as generated images by NRs (NNRs, 10\%, 17\%, and 27\%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for "data-hungry" technologies, such as supervised machine learning approaches, in various clinical applications.}, subject = {Magnetresonanztomografie}, language = {en} } @article{MacedoJavadiHiguchietal.2015, author = {Macedo, Robson and Javadi, Som Mehrbod and Higuchi, Takahiro and Ferreira de Carvalho, Marilia Daniela and Lima Paiva Medeiros, Vanessa de F{\´a}tima and Azevedo, {\´I}talo Medeiros and Lima, Francisco Pignataro and Medeiros, Aldo Cunha}, title = {Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc\(^{99m}\)-sestamibi biodistribition}, series = {Acta Cir{\´u}rgica Brasileira}, volume = {30}, journal = {Acta Cir{\´u}rgica Brasileira}, number = {6}, doi = {10.1590/S0102-865020150060000003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151887}, pages = {388 -- 393}, year = {2015}, abstract = {PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9\(\pm\)0.3\%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0\(\pm\)0.2\% ID/g), control sham group+ simvastatin (1.2\(\pm\)0.3\% ID/g) and control sham group (1.3\(\pm\)0.2\% ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins.}, 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{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{WernerWeichHiguchietal.2017, author = {Werner, Rudolf A. and Weich, Alexander and Higuchi, Takahiro and Schmid, Jan S. and Schirbel, Andreas and Lassmann, Michael and Wild, Vanessa and Rudelius, Martina and Kudlich, Theodor and Herrmann, Ken and Scheurlen, Michael and Buck, Andreas K. and Kropf, Saskia and Wester, Hans-J{\"u}rgen and Lapa, Constantin}, title = {Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach}, series = {Theranostics}, volume = {7}, journal = {Theranostics}, number = {6}, doi = {10.7150/thno.18754}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158008}, pages = {1489-1498}, year = {2017}, abstract = {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.}, subject = {Positronen-Emissions-Tomografie}, language = {en} }