title: Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.
abstract: Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40) is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI), dynamic contrast enhanced magnetic resonance imaging (DCE)-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET) for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13), Avastin (n = 6) or PBS (n = 12). Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09). In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001). There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively). The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Meier
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Rickmer
authors.initials: R
authors.lastname: Braren
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kosanke
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bussemer
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schwarzenböck
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Frank
authors.affiliation: Institute for Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Pieris AG, Freising, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Hohlbaum
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Pieris AG, Freising, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Gille
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Rummeny
authors.affiliation: Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D005260:Female; D019788:Fluorodeoxyglucose F18; D054834:Lipocalins / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D051379:Mice; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D054834:Lipocalins; D019275:Radiopharmaceuticals; C000596016:angiocal protein; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab