Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-14920 Wissenschaftlicher Artikel Chen, Xinyu; Werner, Rudolf A.; Javadi, Mehrbod S.; Maya, Yoshifumi; Decker, Michael; Lapa, Constantin; Herrmann, Ken; Higuchi, Takahiro Radionuclide imaging of neurohormonal system of the heart Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included. 2015 545-558 Theranostics 5 6 urn:nbn:de:bvb:20-opus-149205 10.7150/thno.10900 Klinik und Poliklinik für Nuklearmedizin OPUS4-13954 Wissenschaftlicher Artikel Kläsner, Benjamin; Buchmann, Niels; Gempt, Jens; Ringel, Florian; Lapa, Constantin; Krause, Bernd Joachim Early [\(^{18}\)F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [\(^{18}\)F]O-(2-[\(^{18}\)F]-fluoroethyl)-L-tyrosine ([\(^{18}\)F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [\(^{18}\)F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [\(^{18}\)F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [\(^{18}\)F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [\(^{18}\)F]FET-PET seems to be feasible. 2015 e0141153 PLoS One 10 10 urn:nbn:de:bvb:20-opus-139549 10.1371/journal.pone.0141153 Klinik und Poliklinik für Nuklearmedizin OPUS4-12549 Wissenschaftlicher Artikel Lapa, Constantin; Linsenmann, Thomas; Lückerath, Katharina; Samnick, Samuel; Herrmann, Ken; Stoffer, Carolin; Ernestus, Ralf-Ingo; Buck, Andreas K.; Löhr, Mario; Monoranu, Camelia-Maria Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy? Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. Methods 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. Results The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. Conclusion SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM. 2015 e0122269 PLoS One 10 3 urn:nbn:de:bvb:20-opus-125498 10.1371/journal.pone.0122269 Klinik und Poliklinik für Nuklearmedizin OPUS4-14868 Wissenschaftlicher Artikel Lückerath, Katharina; Lapa, Constantin; Albert, Christa; Herrmann, Ken; Jörg, Gerhard; Samnick, Samuel; Einsele, Herrmann; Knop, Stefan; Buck, Andreas K. \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future. 2015 8418-8429 Oncotarget 6 10 urn:nbn:de:bvb:20-opus-148688 10.18632/oncotarget.3053 Klinik und Poliklinik für Nuklearmedizin OPUS4-14873 Wissenschaftlicher Artikel Philipp-Abbrederis, Kathrin; Herrmann, Ken; Knop, Stefan; Schottelius, Margret; Eiber, Matthias; Lückerath, Katharina; Pietschmann, Elke; Habringer, Stefan; Gerngroß, Carlos; Franke, Katharina; Rudelius, Martina; Schirbel, Andreas; Lapa, Constantin; Schwamborn, Kristina; Steidle, Sabine; Hartmann, Elena; Rosenwald, Andreas; Kropf, Saskia; Beer, Ambros J; Peschel, Christian; Einsele, Hermann; Buck, Andreas K; Schwaiger, Markus; Götze, Katharina; Wester, Hans-Jürgen; Keller, Ulrich In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. 2015 477-487 EMBO Molecular Medicine 7 4 urn:nbn:de:bvb:20-opus-148738 10.15252/emmm.201404698 Klinik und Poliklinik für Nuklearmedizin