@inproceedings{WernerHayakawaAriasLozaetal.2017,
  author    = {Werner, Rudolf and Hayakawa, Nobuyuki and Arias-Loza, Paula-Anah and Wakabayashi, Hiroshi and Shinaji, Tetsuya and Lapa, Constantin and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Bildgebung der fr{\"u}hen linksventrikul{\"a}ren Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell},
  series = {Nuklearmedizin},
  volume    = {56},
  booktitle = {Nuklearmedizin},
  number    = {2},
  publisher = {Schattauer Verlag},
  issn      = {0029-5566},
  doi       = {10.3413/Nukmed-0880-17-02},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161396},
  pages     = {Abstract Nr.: V119},
  year      = {2017},
  abstract  = {Einleitung: Die linksventrikul{\"a}re diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann. Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG {\"u}ber die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikul{\"a}re Ejektionsfraktion (EF) und die Peak F{\"u}llrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Gr{\"o}ße des Rattenherzes angepasst wurde. Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, best{\"a}tigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1\%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.). Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der fr{\"u}hen diabetischen Kardiomyopathie nachgewiesen werden.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {de}
}
@article{LapaAriasLozaHayakawaetal.2017,
  author    = {Lapa, Constantin and Arias-Loza, Paula and Hayakawa, Nobuyuki and Wakabayashi, Hiroshi and Werner, Rudolf A. and Chen, Xinyu and Shinaji, Tetsuya and Herrmann, Ken and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-17148-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159066},
  pages     = {16795},
  year      = {2017},
  abstract  = {Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.},
  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}
}
@inproceedings{WernerWakabayashiJahnsetal.2017,
  author    = {Werner, Rudolf and Wakabayashi, Hiroshi and Jahns, Roland and Erg{\"u}n, S{\"u}leyman and Jahns, Valerie and Higuchi, Takahiro},
  title     = {PET-Guided Histological Characterization of Myocardial Infiltrating Cells in a Rat Model of Myocarditis},
  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/jex071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161127},
  pages     = {i1-i3},
  year      = {2017},
  abstract  = {No abstract available.},
  subject      = {Myokarditis},
  language  = {en}
}
@inproceedings{WernerChenLapaetal.2017,
  author    = {Werner, Rudolf and Chen, Xinyu and Lapa, Constantin and Robinson, Simon and Higuchi, Takahiro},
  title     = {Intracellular behavior of the novel sympathetic nerve agent \(^{18}\)F-LMI1195},
  series = {Journal of Nuclear Cardiology},
  volume    = {24},
  booktitle = {Journal of Nuclear Cardiology},
  number    = {4 Supplement (2017) Aug},
  issn      = {1071-3581},
  doi       = {10.1007/s12350-017-0984-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161137},
  pages     = {1461-1496},
  year      = {2017},
  abstract  = {No abstract available.},
  subject      = {Herz},
  language  = {en}
}
@inproceedings{WernerHiguchiMueggeetal.2017,
  author    = {Werner, Rudolf and Higuchi, Takahiro and Muegge, Dirk and Javadi, Mehrbod S. and M{\"a}rkl, Bruno and Aulmann, Christoph and Buck, Andreas K. and Fassnacht, Martin and Lapa, Constantin and Kreissl, Michael C.},
  title     = {Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment},
  series = {Journal of Nuclear Medicine},
  volume    = {58},
  booktitle = {Journal of Nuclear Medicine},
  number    = {no. supplement 1},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161147},
  pages     = {169},
  year      = {2017},
  abstract  = {Introduction: The prognosis of medullary thyroid carcinoma (MTC) is poor using common chemotherapeutic approaches. However, during the last years encouraging results of recently introduced tyrosine kinase inhibitors (TKI) such as vandetanib have been published. In this study we aimed to correlate the results of \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG) positron emission tomography (PET) imaging with treatment outcome. Methods: Eighteen patients after thyroidectomy with recurrent/advanced MTC lesions receiving vandetanib (300 mg orally/day) could be analysed. A baseline \(^{18}\)F-FDG PET prior to and a follow-up \(^{18}\)F-FDG PET 3 months after TKI initiation were performed. During follow-up, tumor progression was assessed every 3 months including computed tomography according to RECIST. Progression-free survival (PFS) was correlated with the maximum standardized uptake value of \(^{18}\)F-FDG in lymph nodes (SUV(LN)max) or visceral metastases (SUV(MTS)max) as well as with clinical parameters using ROC analysis. Results: Within median 3.6 years of follow-up, 9 patients showed disease progression at median 8.5 months after TKI initiation. An elevated glucose consumption assessed by baseline \(^{18}\)F-FDG PET (SUV(LN)max > 7.25) could predict a shorter PFS (2 y) with an accuracy of 76.5\% (SUV(LN)max <7.25, 4.3 y; p=0.03). Accordingly, preserved tumor metabolism in the follow-up PET (SUV(MTS)max >2.7) also demonstrated an unfavorable prognosis (accuracy, 85.7\%). On the other hand, none of the clinical parameters reached significance in response prediction. Conclusions: In patients with advanced and progressive MTC, tumors with higher metabolic activity at baseline are more aggressive and more prone to progression as reflected by a shorter PFS; they should be monitored more closely. Preserved glucose consumption 3 months after treatment initiation was also related to poorer prognosis.},
  language  = {en}
}
@inproceedings{WernerLapaBucketal.2017,
  author    = {Werner, Rudolf and Lapa, Constantin and Buck, Andreas and Lassmann, Michael and H{\"a}nscheid, Heribert},
  title     = {Less is sometimes more - Accurate Dose Mapping after Endoradiotherapy with \(^{177}\)Lu-DOTATATE/-TOC by One-Single Measurement after 96 h},
  series = {Journal of Nuclear Medicine},
  volume    = {58},
  booktitle = {Journal of Nuclear Medicine},
  number    = {No. Supplement 1},
  publisher = {Society of Nuclear Medicine and Molecular Imaging},
  issn      = {0161-5505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161168},
  pages     = {247},
  year      = {2017},
  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}
}
@article{LapaHerrmannSchirbeletal.2017,
  author    = {Lapa, Constantin and Herrmann, Ken and Schirbel, Andreas and H{\"a}nscheid, Heribert and L{\"u}ckerath, Katharina and Schottelius, Margret and Kircher, Malte and Werner, Rudolf A. and Schreder, Martin and Samnick, Samuel and Kropf, Saskia and Knop, Stefan and Buck, Andreas K. and Einsele, Hermann and Wester, Hans-Juergen and Kort{\"u}m, K. Martin},
  title     = {CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma},
  series = {Theranostics},
  volume    = {7},
  journal   = {Theranostics},
  number    = {6},
  doi       = {10.7150/thno.19050},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172095},
  pages     = {1589-1597},
  year      = {2017},
  abstract  = {C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.},
  language  = {en}
}
@article{WernerSheikhbahaeiJonesetal.2017,
  author    = {Werner, Rudolf A. and Sheikhbahaei, Sara and Jones, Krystyna M. and Javadi, Mehrbod S. and Solnes, Lilja B. and Ross, Ashley E. and Allaf, Mohamad E. and Pienta, Kenneth J. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro and Pomper, Martin G. and Gorin, Micheal A. and Rowe, Steven P.},
  title     = {Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia},
  series = {Annals of Nuclear Medicine},
  volume    = {31},
  journal   = {Annals of Nuclear Medicine},
  number    = {9},
  issn      = {0914-7187},
  doi       = {10.1007/s12149-017-1201-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166971},
  pages     = {696-702},
  year      = {2017},
  abstract  = {Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL. Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean). Results: Overall, 95 of 98 (96.9\%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4\%), followed by the cervical ganglia (51/76, 67.1\%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80\%) and cervical 30/51 (58.8\%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8\%) of the analyzed stellate ganglia and in 45/76 (59.2\%) of the celiac ganglia, whereas only 5/76 (6.6\%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9\%) and cervical ganglia (19/ 22, 86.4\%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts. Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients' cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}