Radioiodinated ligands for the estrogen receptor: tissue distribution of 17 alpha-[125I]iodovinylestradiol derivatives in normal and tumor-bearing adult female rats.
A series of three 125I-labeled 17 alpha-iodovinylestradiol derivatives previously demonstrated to have a selectivity for estrogen receptor tissues in immature female rats were selected for further evaluation in adult female rats. In normal adult female rats, the iodovinyl analogs of moxestrol (IV beta ME2), and moxestrol-3-O methyl ether (IV beta ME2-3-OMe) demonstrated high uterine uptake (0.296-0.437 and 0.135-0.199%ID-kg/g) and selectivity (10-18:1) over the 6 h time period. Subsequent evaluation in two tumor models indicated that [125I]V beta ME2 also possessed the highest tumor uptake and selectivity in the adult female rats bearing the estrogen responsive 9,10-dimethyl-1,2-benzanthracene(DMBA)-induced mammary tumors and that this was receptor mediated. An estrogen independent tumor, the transplanted Walker 256 mammary adenocarcinoma, showed no selectivity of radioligand uptake compared with nontarget tissues. The results suggest the applicability of this agent to the in vivo detection and characterization of estrogen responsive tumors in man.
Hanson
R N
RN
Department of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Franke
L A
LA
Kaplan
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002279:Carcinoma 256, Walker / Q000032:analysis / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000502:physiology; D005260:Female; D007457:Iodine Radioisotopes; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000139:chemically induced / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000032:analysis / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; C034555:17 alpha-iodovinylestradiol; C042987:17-iodovinylestradiol-3-methyl ether; C042716:17 alpha-iodovinyl-11 beta-methoxyestradiol