6-ALPHA-[F-18]FLUOROPROGESTERONE - SYNTHESIS VIA HALOFLUORINATION-OXIDATION, RECEPTOR-BINDING AND TISSUE DISTRIBUTION

We have evaluated 6 alpha-[F-18]fluoroprogesterone as a potential imag ing agent for progesterone receptor (PgR)-positive breast cancer. 6 al pha-Fluoroprogesterone (1) was obtained via halofluorination of the C- 5 double bond in pregnenolone, followed by oxidation of the 3 beta-OH group, elimination of HBr from C-4,5, and epimerization at the C-6 cen ter. The relative binding affinity (RBA) of 6 alpha-fluoroprogesterone (1) to PgR is 11 (R5020 = 100), and its binding selectivity index (BS I, i.e. the ratio of the RBA to the non-specific binding, NSB) is 14.4 ; these values are similar to those of progesterone. 17 alpha-Acetoxy- 6 alpha-fluoroprogesterone (2) was also prepared by the same method, b ut was not used for fluorine-18 labeling studies because its binding a ffinity for PgR is very low (0.9). The synthesis of 1 was adapted to f luorine-18 labeling and although the overall radiochemical yield was l ow (decay-corrected, 0.3%), progestin [F-18]1 was obtained in moderate ly high effective specific activity (147 Ci/mmol). In vivo distributio n studies using estrogen primed immature female rats show that 6 alpha -fluoroprogesterone ([F-18]1) has low uterine uptake, low target tissu e selectivity, and high fat uptake, presumably due to its low RBA and BSI. High uptake in bone, which indicates extensive metabolic defluori nation, suggests that the C-6 position of steroids may not be a good s ite for fluorine-18 labeling.