Rapid liver metabolism, urinary and biliary excretion, and enterohepatic circulation of 16 alpha-radioiodo-17 beta-estradiol.
The radiohalogenated estrogen 16 alpha-[123I]iodo-17 beta-estradiol ([123I]E2) is emerging as a diagnostic tool for imaging of ER-rich malignant tumors, with potential application for site-directed radiotherapy. Clinical use requires an accurate accounting for the biodistribution of the radioactivity, including an assessment of its enterohepatic circulation. We investigated the metabolism and circulation of [125I]E2 in the enterohepatic system in swine, a pharmacokinetic model that resembles humans. With indicator dilution methods, we found that, after its injection into the portal vein, more than 99% of [125I]E2 was cleared from the blood by the liver during the first pass. Water-soluble metabolites were then partly released into the blood and partly excreted into bile. After injection of [125I]E2 into the external jugular vein, one-third of the radioactivity was excreted in bile and two-thirds in the urine. More than 90% of the radioactivity in urine and bile was that of [125I]E2-glucuronide or [125I]E2-sulfate; only a very small fraction of the excreted radioactivity was from free 125I. Radioactivity in bile collected from one swine after i.v. injection of [125I]E2, and then infused into the proximal duodenum of a second swine, was almost totally absorbed during passage through the intestine at 5-7 hr after infusion. The reabsorbed radioactivity was cleared in the urine.
Department of Obstetrics and Gynecology, Chicago Lying-in Hospital, University of Chicago, IL 60637-1470.
A
A
Scharl
M W
MW
Beckmann
J E
JE
Artwohl
S
S
Kullander
J A
JA
Holt
D000818:Animals; D001646:Bile / Q000378:metabolism*; D004764:Enterohepatic Circulation; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism*; D013552:Swine
D007457:Iodine Radioisotopes; D004958:Estradiol; C024871:16 alpha-iodoestradiol