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

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 F-18-AlF- (aluminum-fluoride) and Cu-64-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 Cu-64 or F-18-AlF and then evaluated in a subcutaneous PCa xenograft model (P03) by small-animal PET imaging and biodistribution studies. Results: NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with Cu-64 and F-18-AlF. Cu-64- and F-18-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. Cu-64-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. F-18-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 F-18-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.