@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}
}
@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{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}
}
@article{FroehlichSerflingHiguchietal.2021,
  author    = {Fr{\"o}hlich, Matthias and Serfling, Sebastian and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Schmalzing, Marc and Tony, Hans-Peter and Gernert, Michael and Strunz, Patrick-Pascal and Portegys, Jan and Schwaneck, Eva-Christina and Gadeholt, Ottar and Weich, Alexander and Buck, Andreas K. and Bley, Thorsten A. and Guggenberger, Konstanze V. and Werner, Rudolf A.},
  title     = {Whole-Body [\(^{18}\)F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease},
  series = {Diagnostics},
  volume    = {11},
  journal   = {Diagnostics},
  number    = {11},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics11112073},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250227},
  year      = {2021},
  abstract  = {The 2-deoxy-d-[\(^{18}\)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [\(^{18}\)F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [\(^{18}\)F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [\(^{18}\)F]FDG PET/CT, 22/34 (64.7\%) of patients did not have an established diagnosis, whereas in 7/34 (20.6\%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7\%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [\(^{18}\)F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9\%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5\%) and PMR in the remaining 6/34 (17.6\%). As such, [\(^{18}\)F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4\%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95\%CI, 0.95-1.1) vs. PMR, 0.92 ± 0.1 (95\%CI, 0.85-0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95\%CI, 0.95-1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95\%CI, 0.83-1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95\%CI, 0.55-0.61)) and GCA + PMR (0.64 ± 0.09 (95\%CI, 0.57-0.71); p < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [\(^{18}\)F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases.},
  language  = {en}
}
@article{HartrampfKrebsPeteretal.2022,
  author    = {Hartrampf, Philipp E. and Krebs, Markus and Peter, Lea and Heinrich, Marieke and Ruffing, Julia and Kalogirou, Charis and Weinke, Maximilian and Brumberg, Joachim and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A. and Seitz, Anna Katharina},
  title     = {Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach},
  series = {Biology},
  volume    = {11},
  journal   = {Biology},
  number    = {5},
  issn      = {2079-7737},
  doi       = {10.3390/biology11050660},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271191},
  year      = {2022},
  abstract  = {Simple Summary The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT. Abstract (1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.},
  language  = {en}
}
@article{WernerMarcusSheikhbahaeietal.2018,
  author    = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Solnes, Lilja B. and Leal, Jeffrey P. and Du, Yong and Rowe, Steven P. and Higuchi, Takahiro and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.},
  title     = {Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging},
  series = {Clinical Nuclear Medicine},
  volume    = {44},
  journal   = {Clinical Nuclear Medicine},
  number    = {1},
  issn      = {1536-0229},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168181},
  year      = {2018},
  abstract  = {PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5\%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7\%, ĸ = 0.75) compared to semiquantification (86.2\%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.},
  subject      = {SPECT},
  language  = {en}
}
@article{KhatriChungWerneretal.2021,
  author    = {Khatri, Wajahat and Chung, Hyun Woo and Werner, Rudolf A. and Leal, Jeffrey P. and Pienta, Kenneth J. and Lodge, Martin A. and Gorin, Michael A. and Pomper, Martin G. and Rowe, Steven P.},
  title     = {Effect of point-spread function reconstruction for indeterminate PSMA-RADS-3A lesions on PSMA-targeted PET imaging of men with prostate cancer},
  series = {Diagnostics},
  volume    = {11},
  journal   = {Diagnostics},
  number    = {4},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics11040665},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236528},
  year      = {2021},
  abstract  = {Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is emerging as an important modality for imaging patients with prostate cancer (PCa). As with any imaging modality, indeterminate findings will arise. The PSMA reporting and data system (PSMA-RADS) version 1.0 codifies indeterminate soft tissue findings with the PSMA-RADS-3A moniker. We investigated the role of point-spread function (PSF) reconstructions on categorization of PSMA-RADS-3A lesions. Methods: This was a post hoc analysis of an institutional review board approved prospective trial. Around 60 min after the administration of 333 MBq (9 mCi) of PSMA-targeted \(^{18}\)F-DCFPyL, patients underwent PET/computed tomography (CT) acquisitions from the mid-thighs to the skull vertex. The PET data were reconstructed with and without PSF. Scans were categorized according to PSMA-RADS version 1.0, and all PSMA-RADS-3A lesions on non-PSF images were re-evaluated to determine if any could be re-categorized as PSMA-RADS-4. The maximum standardized uptake values (SUVs) of the lesions, mean SUVs of blood pool, and the ratios of those values were determined. Results: A total of 171 PSMA-RADS-3A lesions were identified in 30 patients for whom both PSF reconstructions and cross-sectional imaging follow-up were available. A total of 13/171 (7.6\%) were re-categorized as PSMA-RADS-4 lesions with PSF reconstructions. A total of 112/171 (65.5\%) were found on follow-up to be true positive for PCa, with all 13 of the re-categorized lesions being true positive on follow-up. The lesions that were re-categorized trended towards having higher SUV\(_{max}\)-lesion and SUV\(_{max}\)-lesion/SUV\(_{mean}\)-blood-pool metrics, although these relationships were not statistically significant. Conclusions: The use of PSF reconstructions for \(^{18}\)F-DCFPyL PET can allow the appropriate re-categorization of a small number of indeterminate PSMA-RADS-3A soft tissue lesions as more definitive PSMA-RADS-4 lesions. The routine use of PSF reconstructions for PSMA-targeted PET may be of value at those sites that utilize this technology.},
  language  = {en}
}
@unpublished{NoseWernerUedaetal.2018,
  author    = {Nose, Naoko and Werner, Rudolf A. and Ueda, Yuichiro and G{\"u}nther, Katharina and Lapa, Constantin and Javadi, Mehrbod S. and Fukushima, Kazuhito and Edenhofer, Frank and Higuchi, Takahiro},
  title     = {Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay},
  series = {International Journal of Cardiology},
  journal   = {International Journal of Cardiology},
  issn      = {0167-5273},
  doi       = {10.1016/j.ijcard.2018.06.089},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163320},
  year      = {2018},
  abstract  = {Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.},
  subject      = {Stammzelle},
  language  = {en}
}
@article{WernerHaenscheidLealetal.2018,
  author    = {Werner, Rudolf and H{\"a}nscheid, Heribert and Leal, Jeffrey P. and Javadi, Mehrbod S. and Higuchi, Takahiro and Lodge, Martin A. and Buck, Andreas K. and Pomper, Martin G. and Lapa, Constantin and Rowe, Steven P.},
  title     = {Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170280},
  pages     = {1-9},
  year      = {2018},
  abstract  = {Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden. Procedures: Of the 44 included patients, 36/44 (82\%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2\%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3\%) vs. higher TBU (>7\%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.},
  subject      = {Positronen-Emissions-Tomografie},
  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}
}