title: Automated synthesis of 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) for estrogen receptor imaging by positron emission tomography.
abstract: 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.
authors.affiliation: Sherbrooke Molecular Imaging Center (CIMS), Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Naseem
authors.initials: N
authors.lastname: Ahmed
authors.forename: Rejean
authors.initials: R
authors.lastname: Langlois
authors.forename: Serge
authors.initials: S
authors.lastname: Rodrigue
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
mesh_terms: D001331:Automation; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006868:Hydrolysis; D007202:Indicators and Reagents; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C521829:11-methoxy-4,16-difluoroestradiol; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D004958:Estradiol