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 gastrinreleasingpeptidereceptor(GRPr),whichishighlyoverexpressed on prostate cancer cells. In the present study, we developed an 18 F-labeled bombesin analog, 18 F-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 ( 19 F) standard of the bombesin analogforbindingaffinityandselectivity forGRPr.Thestabilityof 18 F-BAY 86-4367 was determined in murine and human plasma. Invivo,thetumor-targetingpotentialandpharmacokineticprofile of the 18 F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor–bearing mice. Results: The nonradioactive ( 19 F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability ofthetracerinmurineandhumanplasmawasfoundtobehigh.In 2 prostate cancer xenograft models (PC-3 and LNCaP), 18F-BAY 86-4367showedmorespecificandeffectiveGRPr-basedtargeting in vivo than the benchmark radiotracers 18 F-fluoroethylcholine and 18 F-FDG. In addition, rapid tumor targeting and fast renalexcretion(;70%)andhepatobiliaryexcretion(;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 effectivetumortargetingby 18 F-BAY86-4367suggestthataclinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.