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 Academic Article uri icon


MeSH Major

  • Fluorine Radioisotopes
  • Hydrocarbons, Fluorinated
  • Misonidazole


  • 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.

publication date

  • April 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC4072420

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2011.02.026

PubMed ID

  • 21398131

Additional Document Info

start page

  • 2287

end page

  • 97


  • 19


  • 7