Molecular Imaging of Gastrin-Releasing Peptide Receptor-Positive Tumors in Mice Using 64Cu- and 86Y-DOTA-(Pro1,Tyr4)-Bombesin(1-14)
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- 作者：Grá ; inne B. Biddlecombe ; Buck E. Rogers ; Monique de Visser ; Jesse J. Parry ; Marion de Jong ; Jack L. Erion ; Jason S. Lewis
- 刊名：Bioconjugate Chemistry
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：18
- 期：3
- 页码：724 - 730
- 全文大小：213K
- 年卷期：v.18,no.3(May 2007)
- ISSN：1520-4812
文摘
Bombesin is a tetradecapeptide neurohormone that binds to gastrin-releasing peptide receptors (GRPR). GRPRshave 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 undertakento evaluate radiolabeled MP2346 as a positron emission tomography (PET) imaging agent. MP2346 wasradiolabeled, in high radiochemical purity, with the positron-emitting nuclides 64Cu (t1/2 = 12.7 h, 
chars/beta2.gif" BORDER=0 ALIGN="middle">+ = 19.3%,Eavg = 278 keV) and 86Y (t1/2 = 14.7 h, chars/beta2.gif" BORDER=0 ALIGN="middle">+ = 33%, Eavg = 664 keV). 64Cu-MP2346 and 86Y-MP2346 werestudied 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 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 blockade. 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 models of prostate cancer for the delineation of the GRPR-rich tumors and warrants furtherinvestigation.
chars/beta2.gif" BORDER=0 ALIGN="middle">+ = 19.3%,Eavg = 278 keV) and 86Y (t1/2 = 14.7 h, chars/beta2.gif" BORDER=0 ALIGN="middle">+ = 33%, Eavg = 664 keV). 64Cu-MP2346 and 86Y-MP2346 werestudied 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 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 blockade. 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 models of prostate cancer for the delineation of the GRPR-rich tumors and warrants furtherinvestigation.