20-[¹⁸F]fluoromibolerone, a positron-emitting radiotracer for androgen receptors: Synthesis and tissue distribution studies

To develop an androgen receptor-based, positron-emitting imaging agent for prostate tumors, we have prepared 20-fluoromibolerone (F-Mib) and evaluated its tissue distribution. This compound was synthesized in eight steps from 7α-methyl-19-nortestosterone, with fluorine introduced in the penultimate step by fluoride ion displacement on a spirocyclic sulfate. Fluoromibolerone was obtained in 9%-19% radiochemical yield (decay corrected), at 1.5 hr after bombardment, with an effective specific activity of 217-283 Ci/mmol. The relative binding affinity of F-Mib is 53 (versus R1881 = 100 or mibolerone = 118). In tissue distribution studies in diethylstilbestrol-treated male rats, ¹⁸F-Mib demonstrates high target/tissue uptake efficiency and selectivity: the prostate uptake at 0.5 hr and 4 hr is 1.0%-1.3% injected dose/gram tissue (ID/g) and 0.5%-0.6% ID/g, respectively; the prostate-to-blood and the prostate-to-muscle (non-target) ratios are both ca. 4 at 0.5 hr, and increase to ca. 12 by 4 hr after injection. The observed distribution of ¹⁸F-Mib suggests that it may be useful for in vivo imaging of prostatic tumors in man by positron emission tomography.