Novel multifunctional 18 F-labelled PET tracer with prostate-specific membrane antigen-targeting and hypoxia-sensitive moieties

Abstract

Prostate cancer is one of the most frequently found cancers in men worldwide. Prostate-specific membrane antigen (PSMA) is typically highly expressed in prostate cancer, and the Glu-Urea-Lys (GUL) structure has recently received considerable attention as a key unit of PSMA-targeting agents. Additionally, one of the common characteristics of many solid tumors, such as prostate cancer, is hypoxia. In this study, novel multifunctional PSMA inhibitors containing a PSMA-targeting moiety either with or without a hypoxia-sensitive moiety (F-18-PEG(3)-ADIBOT-2NI-GUL and F-18-PEGS-ADIBOT-GUL, respectively; ADIBOT: azadibenzocyclooctatriazole, 2N1: 2-nitroimidazole) were designed and synthesized, and their feasibility as PET tracers for prostate cancer imaging studies was examined. The compounds labelled with F-18 via the copper-free click reaction were stable in human serum and showed nanomolar binding affinities in in vitro PSMA binding assays. Micro-PET and biodistribution studies indicate that both F-18-labelled inhibitors successfully accumulated in prostate cancer regions, and F-18-PEGS-ADIBOT-2NI-GUL showed a 2-fold higher tumor-to-total non-target organ ratio than that of F-18-PEGS-ADIBOT-GUL, suggesting that the synergistic effects of the PSMA-targeting GUL moiety and the hypoxia-sensitive 2-nitroimidazole moiety can increase tumor uptake of the novel PET tracers in prostate cancer. These findings suggest that this novel multifunctional PET tracer with an F-18-labelled PSMA inhibitor and a 2-nitroimidazole moiety is a potent candidate to provide better diagnosis of prostate cancer via PET imaging studies. (C) 2020 Elsevier Masson SAS. All rights reserved.