Radioiodinated ligands for the estrogen receptor: effect of 3-o-methylation on tissue distribution.
The 3-o-methyl ethers of 17 alpha-[125I]iodovinylestradiol and 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol were prepared in 95% and 89% isolated yields, respectively, at the no-carrier-added level from the corresponding (tri-n-butystannyl)-vinyl intermediates. The new radioligands were evaluated in immature female rats to determine their uptake in, and selectivity for, estrogen-receptor-containing tissues. At 0.5-6 hr after administration, both agents showed preferential uptake and retention by the target tissue. The values for the 11 beta-methoxy derivative, however, were significantly better than those of the 11-unsubstituted compound. Compared with the parent 3-hydroxy radioligands, the [125I]VE2-3-o-Me had lower uptake and target-to-blood ratios at all time periods, but by 6 hr the [125I]VME2-3-o-Me compound showed as high an uptake in the uterus and higher uterus-to-blood ratios. This may be related to metabolic cleavage of the 3-o-methyl group generating the parent compound, which is then sequestered by the target tissue. The results suggest that iodine-123-labeled VME2-3-o-Me would be a good candidate for in vivo gamma imaging of estrogen-containing tissues.
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008024:Ligands; D008745:Methylation; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D008024:Ligands; D011960:Receptors, Estrogen; D004958:Estradiol; C042987:17-iodovinylestradiol-3-methyl ether; C042988:17-iodovinyl-11-methoxyestradiol-3-methyl ether