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18F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging

By Min Yang, Haokao Gao, Yaru Zhou, Ying Ma, Qimeng Quan, Lixin Lang, Kai Chen, Gang Niu, Yongjun Yan and Xiaoyuan Chen

Abstract

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

Topics: Research Paper
Publisher: Ivyspring International Publisher
OAI identifier: oai:pubmedcentral.nih.gov:3086613
Provided by: PubMed Central

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