A Comparative Study of Radiolabeled Bombesin Analogs for the PET Imaging of Prostate Cancer

Journal of Nuclear Medicine

Jinbo Li¹  Hongguang Liu¹  Kai Cheng¹  Mei Tian¹  Hong Zhang¹  Yang Liu¹  Lihong Bu¹  Xiang Hu¹  Xiaowei Ma¹  Zhen Cheng¹ 

关键词: ¹⁸F-AlF;    bombesin;    GRPR;    prostate cancer;    PET;   

DOI  :  10.2967/jnumed.113.121533

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Radiolabeled bombesin (BBN) analogs that bind to the gastrin-releasing peptide receptor (GRPR) represent a topic of active investigation for the development of molecular probes for PET or SPECT of prostate cancer (PCa). RM1 and AMBA have been identified as the 2 most promising BBN peptides for GRPR-targeted cancer imaging and therapy. In this study, to develop a clinically translatable BBN-based PET probe, we synthesized and evaluated 18F-AlF- (aluminum-fluoride) and 64Cu-radiolabeled RM1 and AMBA analogs for their potential application in PET imaging of PCa. Methods: 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)–conjugated RM1 and AMBA were synthesized and tested for their GRPR-binding affinities. The NODAGA-RM1 and NODAGA-AMBA probes were further radiolabeled with 64Cu or 18F-AlF and then evaluated in a subcutaneous PCa xenograft model (PC3) by small-animal PET imaging and biodistribution studies. Results: NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with 64Cu and 18F-AlF. 64Cu- and 18F-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. 64Cu-NODAGA-RM1 exhibited tumor uptake values of 3.3 ± 0.38, 3.0 ± 0.76, and 3.5 ± 1.0 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1.5, and 4 h after injection, respectively. 18F-AlF-NODAGA-RM1 exhibited tumor uptake values of 4.6 ± 1.5, 4.0 ± 0.87, and 3.9 ± 0.48 %ID/g at 0.5, 1, and 2 h, respectively. Conclusion: The high-stability, efficient tumor uptake and optimal pharmacokinetic properties highlight 18F-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.

【 授权许可】

Unknown