title: 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.
abstract: 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 (18)F to expand its role into a bimodal PET/MRI probe. (18)F-Labeling was achieved via a three-step procedure in which 2,2,2-[(18)F]trifluoroethyl p-toluenesulfonate prepared by (18)F-(19)F exchange served as the [(18)F]trifluoroethylating agent. The O-[(18)F]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[(18)F]trifluoroethoxy)propane, with approximately 60% of (18)F incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [(18)F]TFMISO. Approximately 40% of the [(18)F]trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[(18)F]trifluoroethyl iodide failed to produce [(18)F]TFMISO, giving instead 1,1-[(18)F]difluoro-2-iodoethoxy and 1-[(18)F]fluoro-2-iodovinyloxy analogs of [(18)F]TFMISO. Thus, this investigation has identified 2,2,2-[(18)F]trifluoroethyl tosylate as an excellent [(18)F]trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [(18)F]trifluoroethyl ether.
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. msuehiro@usa.net
authors.forename: Makiko
authors.initials: M
authors.lastname: Suehiro
authors.forename: Guangbin
authors.initials: G
authors.lastname: Yang
authors.forename: Geralda
authors.initials: G
authors.lastname: Torchon
authors.forename: Ellen
authors.initials: E
authors.lastname: Ackerstaff
authors.forename: John
authors.initials: J
authors.lastname: Humm
authors.forename: Jason
authors.initials: J
authors.lastname: Koutcher
authors.forename: Ouathek
authors.initials: O
authors.lastname: Ouerfelli
mesh_terms: D000478:Alkylation; D014408:Biomarkers, Tumor / Q000138:chemical synthesis / Q000737:chemistry; D015687:Cell Hypoxia / Q000502:physiology; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis*; D007553:Isotope Labeling; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D010100:Oxygen / Q000737:chemistry; D014105:Tosyl Compounds / Q000138:chemical synthesis
chemical_list: D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D014105:Tosyl Compounds; D008920:Misonidazole; D010100:Oxygen