A comparative study of radiolabeled bombesin analogs for the PET imaging of prostate cancer

Y Liu, X Hu, H Liu, L Bu, X Ma, K Cheng… - Journal of nuclear …, 2013 - Soc Nuclear Med
Y Liu, X Hu, H Liu, L Bu, X Ma, K Cheng, J Li, M Tian, H Zhang, Z Cheng
Journal of nuclear medicine, 2013Soc Nuclear Med
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 …
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.
Society of Nuclear Medicine and Molecular Imaging