title: F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging.
abstract: Radiolabeled bombesin analogs are promising probes for cancer imaging of gastrin-releasing peptide receptor (GRPR). In this study, we developed (18)F-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-NHCH(2)CH(3)) and MATBBN (Gly-Gly-Gly-Arg-Asp-Asn-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH(2)CH(3)), and agonists AGBBN (Gln-Trp-Ala-Val-Gly-His-Leu-MetNH(2)) and MAGBBN (Gly-Gly-Gly-Arg-Asp-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-MetNH(2)) were radiolabeled with (18)F via 4-nitrophenyl 2-(18)F-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 (18)F-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 (18)F-FP-MAGBBN over the antagonist (18)F-FP-MATBBN. Both tracers showed good tumor/background contrast, with the agonist (18)F-FP-MAGBBN having significantly higher tumor uptake than the antagonist (18)F-FP-MATBBN (P < 0.01). In conclusion, Gly-Gly-Gly-Arg-Asp-Asn linker significantly improved the pharmacokinetics of the otherwise hydrophobic BBN radiotracers. (18)F-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.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Yaru
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Quan
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen