QUANTITATIVE WHOLE-BODY AUTORADIOGRAPHY IN PREGNANT RABBITS TO DETERMINE FETAL EXPOSURE OF POTENTIAL TERATOGENIC COMPOUNDS

Whole-body autoradiography (WBA) allows the determination of sites of accumulation and differential distribution of radiolabeled compounds w ithin organs. WBA is routinely conducted in pregnant rats to evaluate placental transfer and fetal distribution of potential developmental t oxins. This technique has recently been adapted to evaluate tissue dis tribution in the pregnant rabbit, which may be a more appropriate mode l for some pharmaceutical candidates. A preliminary WBA study was cond ucted on New Zealand white (NZW) rabbits at gestation day 18, 1 h foll owing a single oral dose of C-14-glucose. The purpose of this study wa s to validate the use of WBA techniques in assessing the placental tra nsfer of compounds in pregnant rabbits. Antiviral compound LY217896 so dium demonstrated developmental toxicity in the pregnant NZW rabbit fo llowing multiple oral doses of 10 mg/kg on gestation days 6 through 18 . WBA techniques were used to determine the distribution of radiocarbo n 30 minutes following a single oral 10-mg/kg dose of C-14-LY217896 so dium in pregnant NZW rabbits on gestation day 18. (C) 1998 Elsevier Sc ience Inc.