MP46-19 MICRODISTRIBUTION OF ALPHA PARTICLE EMITTING RADIUM-223 DICHLORIDE IN MODELS OF PROSTATE CANCER BONE METASTASIS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2015MP46-19 MICRODISTRIBUTION OF ALPHA PARTICLE EMITTING RADIUM-223 DICHLORIDE IN MODELS OF PROSTATE CANCER BONE METASTASIS Diane Abou, David Ulmert, Robert Hobbs, Ryan Riddle, and Daniel Thorek Diane AbouDiane Abou More articles by this author , David UlmertDavid Ulmert More articles by this author , Robert HobbsRobert Hobbs More articles by this author , Ryan RiddleRyan Riddle More articles by this author , and Daniel ThorekDaniel Thorek More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1582AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radium-223 dichloride (Xofigo, Bayer HealthCare Pharmaceuticals) is a first in class alpha particle emitter producing a survival benefit for patients with late stage bone metastatic castrate resistant prostate cancer (bmCRPC). Dosed at 45 kBq per kg every 4 weeks for 6 total injections, the bone seeking radionuclide delivers 4 high-energy alpha particles across a path length of only several cell diameters. Mechanism of action for the survival benefit is not fully understood, hampering our ability to best utilize this novel therapy. We tested 223Ra in naïve and bone metastatic models of disease, to define the whole body and sub-organ distribution of the radionuclide. Our results shed light on important considerations for pre- and clinical evaluation of 223Ra for personalized radiotherapy. METHODS Animals were dosed with 45 kBq per kg of clinical grade 223Ra. Whole body distribution was monitored by gamma counting in multiple skeletally-mature murine models. Organ and whole body retention were assessed at 1, 4 and 24 h. Detailed 223Ra microdistribution was assessed by cross-modality imaging of whole body and long bone autoradiography, histochemistry and alpha-camera imaging of whole-mount, undecalcified tissues. Uptake dependence and radiobiological effect of 223Ra on bone morphology were evaluated by 10 μm isotropic resolution μCT (SkyScan). RESULTS In contrast to previous preclinical work, our distribution studies recapitulate the planar scintigraphy results in man (Carrasquillo et al., EJNMMI, 2013), with 223Ra accumulation observed in bowel, stomach, and spleen. In particular, whole-body autoradiography demonstrated the radioisotope bound to the contents of the digestive organs. Kinetic analysis revealed rapid clearance from the blood, and delayed clearance from kidney and intestine. In the bone, 223Ra predominantly localized to the growth plates; largely sparing the marrow cavity. In bone metastatic models, including the osteoblastic LNCaP, 223Ra uptake was significantly lower than that in the epiphyseal plate (Figure). CONCLUSIONS Here we provide greater understanding of the in vivo biological fate of this radiopharmaceutical, with significant implications for enhanced dosing strategies in bmCRPC. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e551 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diane Abou More articles by this author David Ulmert More articles by this author Robert Hobbs More articles by this author Ryan Riddle More articles by this author Daniel Thorek More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...