Radiolabeled bombesin analogs are promising probes for cancer imaging of gastrin-releasing peptide receptor (GRPR). In this study, we developed 18F-labeled GRPR agonists and antagonists for positron emission tomography (PET) imaging of prostate cancer. GRPR antagonists ATBBN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3) and MATBBN (Gly-Gly-Gly-Arg-Asp-Asn-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3), and agonists AGBBN (Gln-Trp-Ala-Val-Gly-His-Leu-MetNH2) and MAGBBN (Gly-Gly-Gly-Arg-Asp-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-MetNH2) were radiolabeled with 18F via 4-nitrophenyl 2-18F-fluoropropionate. The in vitro receptor binding, cell uptake, and efflux properties of the radiotracers were studied on PC-3 cells. An in vivo PET study was performed on mice bearing PC-3 tumors. Direct 18F-labeling of known GRPR antagonist ATBBN and agonist AGBBN did not result in good tumor targeting or appropriate pharmacokinetics. Modification was made by introducing a highly hydrophilic linker Gly-Gly-Gly-Arg-Asp-Asn. Higher receptor binding affinity, much higher cell uptake and slower washout were observed for the agonist 18F-FP-MAGBBN over the antagonist 18F-FP-MATBBN. Both tracers showed good tumor/background contrast, with the agonist 18F-FP-MAGBBN having significantly higher tumor uptake than the antagonist 18F-FP-MATBBN (P < 0.01). In conclusion, Gly-Gly-Gly-Arg-Asp-Asn linker significantly improved the pharmacokinetics of the otherwise hydrophobic BBN radiotracers. 18F-labeled BBN peptide agonists may be the probes of choice for prostate cancer imaging due to their relatively high tumor uptake and retention as compared with the antagonist counterparts
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