Synthesis and biological evaluation of [18F](2S,4S)4-(3-fluoropropyl)arginine as a tumor imaging agent

Designing novel F-18-labeled amino acid derivatives for targeted amino acid transporters is an attractive strategy for the development of therapeutic and diagnostic agents for cancer therapy. In this work, we have developed a novel 3-fluoropropyl analog of arginine, namely, (2S,4S)4-[F-18]FRPArg, [F-18]1, to be used as a probe for studying arginine metabolism. Optically pure and labeled with F-18 and F-19, (2S,4S)4-(3-fluoropropyl)arginine was synthesized and isolated in high radiochemical purity (>95%). In vitro uptake assays in human MCF-7 cells revealed that [F-18]1 enters cells mainly via sodium-independent cationic amino acid transporters and was inhibited >62% by arginine. [F-18]1 showed a high cellular uptake of 7.3 +/- 0.24% and 6.07 +/- 03% uptake/100 mg protein after incubation in MCF-7 and MDA-MB-231 cells for 120 min, respectively. In vivo biodistribution studies demonstrated that [F-18]1 provided high tumor uptake and high tumor to muscle ratios (5:1 at the 30 and 60 min time points). In vivo PET imaging studies demonstrated tumor-specific uptake in nude mice bearing MCF-7 breast tumors with an excellent tumor-to-muscle ratio. These results suggest that [F-18]1 is a promising tracer for clinical breast cancer imaging and may be used to diagnose and monitor diseases that are associated with arginine metabolism. (C) 2019 Elsevier Masson SAS. All rights reserved.