18F-labelling of A-ring substituted 16α-fluoro-estradiols as potential radiopharmaceuticals for PET imaging

The 2-methoxy derivative of estradiol is currently in Phase II clinical trial as an anticancer agent while the 4-methyl derivative has been shown to interact with cytoplasmic and nuclear estrogen receptors in rat pituitary gland and hypothalamus. We hypothesize that the 16α-18F-analogs of these estrogens could be suitable radiotracers to evaluate action mechanisms of the parent compounds. In this study we report the synthesis of the 16α-18F and 16α-19F-analogs of the A-ring substituted estradiols in high yield via stereoselective opening of the intermediate 16β,17β-O-cyclic sulfones with [18F]F− or F− followed by deprotection.