Automated synthesis of 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) for estrogen receptor imaging by positron emission tomography

Nucl Med Biol. 2007 May;34(4):459-64. doi: 10.1016/j.nucmedbio.2007.02.001.


Addition of both a 4-fluoro and 11beta-methoxy group onto 16alpha-[(18)F]fluoroestradiol ([(18)F]FES) yields 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) with potential improved properties for positron emission tomography (PET) imaging of estrogen receptor densities in breast cancer patients. In order to provide 4F-M[(18)F]FES as a radiopharmaceutical for clinical trials, we developed an automated synthesis procedure using 3-O-methoxymethyl-11beta-methoxy-4-fluoro-16,17-O-sulfuryl-16-epiestriol as precursor. The radio synthesis involves stereoselective opening of the protected cyclic sulfone precursor via nucleophilic fluorination with [(18)F]fluoride in acetonitrile. After removal of the protecting ether and 17beta-sulphate groups by rapid hydrolysis in acidic ethanol and subsequent reversed-phase HPLC purification, the pure 4F-M[(18)F]FES was obtained as a sterile physiological saline solution in 45-50% radiochemical yield (decay corrected). The radiochemical purity of the final product was >98% and the effective specific activity (ESA) of 4F-M[(18)F]FES prepared under optimized conditions was >15,000 Ci/mmol. The total preparation time was 110+/-5 min and the product was shown to be stable for at least 6 h.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Chromatography, High Pressure Liquid
  • Estradiol / analogs & derivatives*
  • Estradiol / chemical synthesis
  • Estradiol / pharmacokinetics
  • Fluorine Radioisotopes / chemistry
  • Hydrolysis
  • Indicators and Reagents
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Estrogen / metabolism*
  • Spectrophotometry, Ultraviolet


  • 11-methoxy-4,16-difluoroestradiol
  • Fluorine Radioisotopes
  • Indicators and Reagents
  • Radiopharmaceuticals
  • Receptors, Estrogen
  • Estradiol