Molecular Imaging of Gastrin-Releasing Peptide Receptor-Positive Tumors in Mice Using 64Cu- and 86Y-DOTA−(Pro1,Tyr4)-Bombesin(1−14)

Bombesin is a tetradecapeptide neurohormone that binds to gastrin-releasing peptide receptors (GRPR). GRPRs have been found in a variety of cancers including invasive breast and prostate tumors. The peptide MP2346 (DOTA−(Pro1,Tyr4)-bombesin(1−14)) was designed to bind to these GRP receptors. This study was undertaken to evaluate radiolabeled MP2346 as a positron emission tomography (PET) imaging agent. MP2346 was radiolabeled, in high radiochemical purity, with the positron-emitting nuclides 64Cu (t 1/2 = 12.7 h, β+ = 19.3%, E avg = 278 keV) and 86Y (t 1/2 = 14.7 h, β+ = 33%, E avg = 664 keV). 64Cu-MP2346 and 86Y-MP2346 were studied in vitro for cellular internalization by GRPR-expressing PC-3 (human prostate adenocarcinoma) cells. Both 64Cu- and 86Y-MP2346 were studied in vivo for tissue distribution in nude mice with PC-3 tumors. Biodistribution in PC3 tumor-bearing mice demonstrated higher tumor uptake, but lower liver retention, in animals injected with 86Y-MP2346 compared to 64Cu-MP2346. Receptor-mediated uptake was confirmed by a significant reduction in uptake in the PC-3 tumor and other receptor-rich tissues by coinjection of a blockade. Small animal PET/CT imaging was carried out in mice bearing PC-3 tumors and rats bearing AR42J tumors. It was possible to delineate PC-3 tumors in vivo with 64Cu-MP2346, but superior 86Y-MP2346-PET images were obtained due to lower uptake in clearance organs and lower background activity. The 86Y analogue demonstrated excellent PET image quality in models of prostate cancer for the delineation of the GRPR-rich tumors and warrants further investigation.