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Tritiated 17 alpha-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17 alpha-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (Kd = 1.96 x 10(-10)M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 hr after injection. After 30 min the uterine uptake was 1.73% dose/g. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23-30% of the uptake in the uterus. Tritiated 17 alpha-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that 17 alpha-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.
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