Radiosynthesis of the tumor hypoxia marker [18F]TFMISO via O-[18F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles

The MRI hypoxia marker trifluoromisonidazole (TFMISO) [1-(2-nitro-1H-imidazol-1-yl)-3-(2,2,2-trifluoroethoxy) propan-2-ol] was successfully labeled with F-18 to expand its role into a bimodal PET/MRI probe. F-18-Labeling was achieved via a three-step procedure in which 2,2,2-[F-18]trifluoroethyl p-toluenesulfonate prepared by F-18-F-19 exchange served as the [F-18]trifluoroethylating agent. The O-[F-18]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[F-18]trifluoroethoxy) propane, with approximately 60% of F-18 incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [F-18] TFMISO. Approximately 40% of the [F-18] trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[F-18] trifluoroethyl iodide failed to produce [F-18] TFMISO, giving instead 1,1-[F-18]difluoro-2-iodoethoxy and 1-[F-18]fluoro-2-iodovinyloxy analogs of [F-18] TFMISO. Thus, this investigation has identified 2,2,2-[F-18] trifluoroethyl tosylate as an excellent [F-18] trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [F-18] trifluoroethyl ether. (C) 2011 Published by Elsevier Ltd.