THE USE OF -METHOXYMETHYL-16-BETA,17-BETA-EPIESTRIOL-O-CYCLIC SULFONEAS THE PRECURSOR IN THE SYNTHESIS OF F-18 16-ALPHA-FLUOROESTRADIOL

We have prepared 3-methoxymethyl-16 beta,17 beta-epiestriol-O-cyclic s ulfone (1c) and used it as a substrate for the production of F-18 16 a lpha-fluoroestradiol, via nucleophilic fluorination with fluoride ion. The compound is straightforward to make from the commercially availab le epiestriol and is a stable crystalline compound that can be stored for at least a year at room temperature. Reaction with fluorine-18 flu oride provides excellent yields; typically >90% incorporation of the f luoride is achieved. Partial purification of the labeled product may b e accomplished at this stage. Hydrolysis of the methoxymethyl protecti ng group and ring-opened sulfate occurs rapidly in ethanolic acid solu tion. In the presence of water the hydrolysis requires more vigorous c onditions and additional time but still proceeds to completion. Labele d fluoroestradiol is isolated at the end of a 1-2 h synthesis, dependi ng on the hydrolysis method of 30-45% chemical (decay corrected) yield with respect to fluoride, with a specific activity >1 Ci per micromol e. Copyright (C) 1996 Elsevier Science Inc.