Synthesis and evaluation of (17.alpha.,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-diol and (17.alpha.,20E)-21-[125I]iodo-11.beta.-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol [17.alpha.-iodovinyl)estradiol derivatives] as high specific activity potential radiopharmaceuticals

Abstract

Two 17.alpha.-[125I]iodovinyl estradiol derivative receptors possessing high specific activity were prepared and tested as potential radiopharmaceuticals [to image breast tumors]. The use of the 3-acetyl derivatives and the replacement of iodine monochloride with sodium iodide and Chloramine-T in THF[tetrahydrofuran]/phosphate buffer (pH 7.0) permitted the synthesis of no-carrier-added (17.alpha.,20E)-221-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (4b) and (17.alpha.,20E)-21-[125I]iodo-11.beta.-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (4d) with 50% radiochemical yield and high purity. Although the specific activity represents only 1/2 of the theoretical value in some cases, this modified approach is a substantial improvement over the previously published method. The preliminary distribution studies indicate that although both 4b and 4b localize in the rat tissues known to have a large concentration of estrogen receptors, 4d accumulates in higher amounts in target tissues and provides a high target to nontarget ratio.