Receptor-binding radiopharmaceuticals for imaging breast tumors: estrogen-receptor interactions and selectivity of tissue uptake of halogenated estrogen analogs.

Four halogenated estrogen analogs--o-fluorohexestrol, and 1-fluoro-, 1-bromo-, and 1-iodohexestrol--have been prepared and tritium-labeled in high specific activity, to investigate their potential as estrogen-receptor-based agents for imaging breast tumors. These compounds bind with high affinity in vitro to the cytoplasmic uterine estrogen receptor from rat and lamb and sediment as 8S receptor complexes on sucrose gradients. After 1 hr in immature rats, these compounds show high uptake into the uterus, but low uptakes (10--25% of the uterine levels) into most nontarget tissues. The uterine uptake is estrogen specific since it is depressed by excess nonradioactive estradiol. Uptake selectivity is greatest for the fluorohexestrols and decreases for the bromo and iodo compounds. In mature rats bearing DMBA-induced mammary tumors, selective uptake by the uterus and tumors is seen with 1-fluoro[3H4]hexestrol and o-fluoro[3H3]hexestrol. The studies indicate that these four halogenated hexestrols are promising candidates as estrogen-receptor-based agents for the imaging of human breast tumors.