TY - JOUR T1 - microPET and Autoradiographic Imaging of GRP Receptor Expression with <sup>64</sup>Cu-DOTA-[Lys<sup>3</sup>]Bombesin in Human Prostate Adenocarcinoma Xenografts JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1390 LP - 1397 VL - 45 IS - 8 AU - Xiaoyuan Chen AU - Ryan Park AU - Yingping Hou AU - Michel Tohme AU - Antranik H. Shahinian AU - James R. Bading AU - Peter S. Conti Y1 - 2004/08/01 UR - http://jnm.snmjournals.org/content/45/8/1390.abstract N2 - Overexpression of gastrin-releasing peptide (GRP) receptor (GRPR) in both androgen-dependent (AD) and androgen-independent (AI) human neoplastic prostate tissues provides an attractive target for prostate cancer imaging and therapy. The goal of this study was to develop 64Cu-radiolabeled GRP analogs for PET imaging of GRPR expression in prostate cancer xenografted mice. Methods: [Lys3]bombesin ([Lys3]BBN) was conjugated with 1,4,7,10-tetraazadodecane-N,N′,N″,N‴-tetraacetic acid (DOTA) and labeled with the positron-emitting isotope 64Cu (half-life = 12.8 h, 19% β+). Receptor binding of DOTA-[Lys3]BBN and internalization of 64Cu-DOTA-[Lys3]BBN by PC-3 prostate cancer cells were measured. Tissue biodistribution, microPET, and whole-body autoradiographic imaging of the radiotracer were also investigated in PC-3 (AI)/CRW22 (AD) prostate cancer tumor models. Results: A competitive receptor- binding assay using 125I-[Tyr4]BBN against PC-3 cells yielded a 50% inhibitory concentration value of 2.2 ± 0.5 nmol/L for DOTA-[Lys3]BBN. Incubation of cells with the 64Cu-labeled radiotracer showed temperature- and time-dependent internalization. At 37°C, &gt;60% of the tracer was internalized within the first 15 min and uptake remained constant for 2 h. Radiotracer uptake was higher in AI PC-3 tumor (5.62 ± 0.08 %ID/g at 30 min after injection, where %ID/g is the percentage of injected dose per gram) than in AD CWR22 tumor (1.75 ± 0.05 %ID/g at 30 min after injection). Significant accumulation of the activity in GRPR-positive pancreas was also observed (10.4 ± 0.15 %ID/g at 30 min after injection). Coinjection of a blocking dose of [Lys3]BBN inhibited the activity accumulation in PC-3 tumor and pancreas but not in CWR22 tumor. microPET and autoradiographic imaging of 64Cu-DOTA-[Lys3]BBN in athymic nude mice bearing subcutaneous PC-3 and CWR22 tumors showed strong tumor-to-background contrast. Conclusion: This study demonstrates that PET imaging of 64Cu-DOTA-[Lys3]BBN is able to detect GRPR-positive prostate cancer. ER -