Bombesin is a tetra
decapepti
de neurohormone that binds to gastrin-releasing pepti
de receptors (GRPR). GRPRshave been found in a variety of cancers including invasive breast and prostate tumors. The pepti
de MP2346(DOTA-(Pro
1,Tyr
4)-bombesin(1-14)) was
designed to bind to these GRP receptors. This study was un
dertakento evaluate radiolabeled MP2346 as a positron emission tomography (PET) imaging agent. MP2346 wasradiolabeled, in high radiochemical purity, with the positron-emitting nucli
des
64Cu (
t1/2 = 12.7 h,
+ = 19.3%,
Eavg = 278 keV) and
86Y (
t1/2 = 14.7 h,
+ = 33%,
Eavg = 664 keV).
64Cu-MP2346 and
86Y-MP2346 werestudied
in vitro for cellular internalization by GRPR-expressing PC-3 (human prostate a
denocarcinoma) cells.Both
64Cu- and
86Y-MP2346 were studied
in vivo for tissue distribution in nu
de mice with PC-3 tumors. Biodistribution in PC3 tumor-bearing mice
demonstrated higher tumor uptake, but lower liver retention, in animalsinjected with
86Y-MP2346 compared to
64Cu-MP2346. Receptor-mediated uptake was confirmed by a significantreduction in uptake in the PC-3 tumor and other receptor-rich tissues by coinjection of a blocka
de. Small animalPET/CT imaging was carried out in mice bearing PC-3 tumors and rats bearing AR42J tumors. It was possibleto
delineate PC-3 tumors
in vivo with
64Cu-MP2346, but superior
86Y-MP2346-PET images were obtained dueto lower uptake in clearance organs and lower background activity. The
86Y analogue
demonstrated excellentPET image quality in mo
dels of prostate cancer for the
delineation of the GRPR-rich tumors and warrants furtherinvestigation.