18F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Bombesin is a peptide exhibiting high affinity for the gastrin-releasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an F-18-labeled bombesin analog, F-18-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer. Methods: In vitro pharmacologic studies were performed to characterize the nonradioactive (F-19) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of F-18-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the F-18 tracer were analyzed with biodistribution experiments and PET studies of prostate tumor-bearing mice. Results: The nonradioactive (F-19) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), F-18-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers F-18-fluoroethylcholine and F-18-FDG. In addition, rapid tumor targeting and fast renal excretion (similar to 70%) and hepatobiliary excretion (similar to 10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice. Conclusion: Favorable preclinical data showing specific and effective tumor targeting by F-18-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.