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

Addition of both a 4-fluoro and 11 beta-methoxy group onto 16 alpha-[F-18]fluoroestradiol ([F-18]FES) yields 11 beta-methoxy-4,16 alpha-[16 alpha-F-18]diF]difluoroestradiol (4F-M[F-18]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[F-18]FES as a radiopharmaceutical for clinical trials, we developed an automated synthesis procedure using 3-O-methoxymethyl-11 beta-methoxy-4-fluoro-16,17-O-sulfuryl-16-epicstriol as precursor. The radio synthesis involves stereoselective opening of the protected cyclic sulfone precursor via nucleophilic fluorination with [F-18]fluoride in acetonitrile. After removal of the protecting ether and 17 beta-sulphate groups by rapid hydrolysis in acidic ethanol and subsequent reversed-phase HPLC purification, the pure 4F-M[F-18]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[F-18]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. (c) 2007 Elsevier Inc. All rights reserved