Article ID Journal Published Year Pages File Type
2593596 Reproductive Toxicology 2013 10 Pages PDF
Abstract

Antibody-like biopharmaceuticals cross the placenta by utilizing transport pathways available for transfer of maternal antibodies to the conceptus. To characterize the timing and magnitude of this transfer in the rat, embryo/fetal biodistribution of maternally administered radiolabeled humanized IgG2 was quantified over the course of gestation using gamma counting and whole body autoradiography. The result was humanized IgG2 found in rat embryo/fetal tissues as early as gestation day 11 with a >1000-fold increase in the amount of total IgG2 by day 21. The concentration of IgG2 in rat embryo/fetal tissues generally remained unchanged from gestation day 11 to 17 with a slight increase from day 17 to 21. In addition, fetal-maternal tissue concentration ratios remained stable during organogenesis with a slight increase from gestation day 17 to 21. Based on the empirical amount of antibody present in the embryo/fetus during specific developmental windows, direct antibody binding to biological targets could potentially result in adverse developmental outcomes.

► IgG2 is present in embryo/fetal tissues (GD 10–21) after a single maternal IV dose. ► Total IgG2 (μg) in embryo/fetal tissue increases >1000-fold between GD 11 and 21. ► IgG2 concentration in embryo/fetal tissue is generally unchanged between GD 11 and 17. ► IgG2 concentration in embryo/fetal tissue increases slightly from GD 17 to 21.

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Life Sciences Environmental Science Health, Toxicology and Mutagenesis
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