title: The use of 3-methoxymethyl-16 beta, 17 beta-epiestriol-O-cyclic sulfone as the precursor in the synthesis of F-18 16 alpha-fluoroestradiol.
abstract: We have prepared 3-methoxymethyl-16 beta, 17 beta-epiestriol-O-cyclic sulfone (1c) and used it as a substrate for the production of F-18 16 alpha-fluoroestradiol, via nucleophilic fluorination with fluoride ion. The compound is straightforward to make from the commercially available epiestriol and is a stable crystalline compound that can be stored for at least a year at room temperature. Reaction with fluorine-18 fluoride provides excellent yields; typically > 90% incorporation of the fluoride is achieved. Partial purification of the labeled product may be accomplished at this stage. Hydrolysis of the methoxymethyl protecting group and ring-opened sulfate occurs rapidly in ethanolic acid solution. In the presence of water the hydrolysis requires more vigorous conditions and additional time but still proceeds to completion. Labeled fluoroestradiol is isolated at the end of a 1-2 h synthesis, depending on the hydrolysis method of 30-45% chemical (decay corrected) yield with respect to fluoride, with a specific activity > 1 Ci per micromole.
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Lim
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: M S
authors.initials: MS
authors.lastname: Berridge
authors.forename: T J
authors.initials: TJ
authors.lastname: Tewson
mesh_terms: D003499:Cyclic S-Oxides; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D004964:Estriol / Q000031:analogs & derivatives*; D005462:Fluorine Radioisotopes; D006868:Hydrolysis; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013997:Time Factors
chemical_list: C105030:3-methoxymethyl-16,17-epiestriol-O-cyclic sulfone; D003499:Cyclic S-Oxides; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D004958:Estradiol; C043436:16-fluoroestradiol; D004964:Estriol