microPET and Autoradiographic Imaging of GRP Receptor Expression with 64Cu-DOTA-[Lys3]Bombesin in Human Prostate Adenocarcinoma Xenografts

Journal of Nuclear Medicine

Yingping Hou¹  Ryan Park¹  James R. Bading¹  Michel Tohme¹  Xiaoyuan Chen¹  Peter S. Conti¹  Antranik H. Shahinian¹ 

[1] PET Imaging Science Center, University of Southern California Keck School of Medicine, Los Angeles, California PET Imaging Science Center, University of Southern California Keck School of Medicine, Los Angeles, California PET Imaging Science Center, University of Southern California Keck School of Medicine, Los Angeles, California

关键词: prostate cancer;    microPET;    gastrin-releasing peptide receptor;    bombesin;    ⁶⁴Cu;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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, >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.

【 授权许可】

Unknown