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.
Two 17 alpha-[125I]iodovinyl estradiol derivatives 4b,d possessing high specific activity have been prepared and tested as potential radiopharmaceuticals. The use of the 3-acetyl derivatives 2c,e and the replacement of iodine monochloride with sodium iodide and Chloramine-T in THF/phosphate buffer (pH 7.0) permitted us to synthesize no-carrier-added (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d iol (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 half of the theoretical value in some cases, this modified approach is a substantial improvement over the previously published method. Our preliminary distribution studies indicate that although both 4b and 4d localize in the 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.
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol; C034555:17 alpha-iodovinylestradiol; C042716:17 alpha-iodovinyl-11 beta-methoxyestradiol