11 beta-methoxy-, 11 beta-ethyl- and 17 alpha-ethynyl-substituted 16 alpha-fluoroestradiols: receptor-based imaging agents with enhanced uptake efficiency and selectivity.

摘要: We have prepared three analogues of 16 alpha-fluoroestradiol (FES) substituted either with an 11 beta-methoxy group (1, beta-MeO-FES), beta-ethyl (2, beta-Et-FES), or a 17 alpha-ethynyl (3, alpha-ethynyl-FES). These substituents all lower the binding FES to serum proteins alphafetoprotein and sex steroid protein, but their effect on estrogen receptor varies: Receptor is increased by groups, decreased group. also parallel lipophilicity, hence nonspecific estimated for these compounds. All compounds were in fluorine-18 labeled form, at effective specific activities 90-1600 Ci/mmol, fluoride ion displacement reactions as done previously FES. Tissue distribution studies immature rats show high uptake selectivity target tissue (uterus) competition excess unlabeled estradiol. Percent injected dose per gram values (% ID/g) 1 h are 6% beta-MeO-FES 11-13% beta-Et-FES alpha-ethynyl-FES (FES itself has % ID/g 9%). Uptake terms uterus blood muscle ratios highest (43-149). Metabolic consumption that most activity unmetabolized rapidly nearly completely metabolized. In muscle, estrogens intermediate levels metabolic consumption; some cases extracts unmetabolized. Thus, cause major alterations nonreceptor affinity, efficiency selectivity, extent metabolism. It not readily clear, however, whether result differences altered patterns Nevertheless, should be useful providing spectrum properties could used imaging different estrogen-receptor-containing structures.