Miriam Rubinchik-Stern^a, Miriam Shmuel^a, Jacob Bar^b, Sara Eyal^a*, and Michal Kovo^b

 ^a Institute for Drug Research, School of Pharmacy, Faculty of Medicine. The Hebrew University, Jerusalem, Israel. ^b Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel

 Introduction: The near-infrared probe indocyanine green (ICG) imaging dye is used mostly for ophthalmic angiography. Pregnant women might also be exposed to ICG, thus we aimed to characterize its transfer across the placenta using the placental perfusion model.

Methods: Placentas were obtained from caesarean deliveries at term and selected cotyledons were cannulated and dually perfused. ICG, 9.6 µg/mL and a permeability reference marker, antipyrine (50 μg/mL), were added to the maternal circulation in the absence (n=4) or the presence of the organic anion transporting polypeptide (OATPs) inhibitors rifampin (10 µg/mL mg/mL; n=5) or the P-glycoprotein inhibitor valspodar (2 µg/mL; n=3). Maternal-to-fetal transfer of ICG was evaluated over 180 min. Placental integrity and viability were determined by measuring the flow rates, fetal artery inflow pressure, and β-hCG production during the experiments.

Results: ICG’s maternal-to-fetal transfer was slow and the cumulative percent of the probe in the fetal reservoir was minor. Rifampin did not significantly affect ICG’s accumulation (1.9±0.5% and 1.2±0.4%, for control and rifampin-treated placentas, respectively; p>0.05). However, when ICG transfer was normalized to that of antipyrine (transfer index), it was lower in the presence of rifampin (a 41% decrease; p<0.05), suggesting the involvement of placental organic anion transporting polypeptides (OATPs). Valspodar did not appear to modify the placental kinetics of ICG.

Discussion: ICG’s maternal-to-fetal transfer across term placentas is minimal and is likely mediated, at least in part, by OATPs. Under normal conditions, the human placenta is an effective protective barrier to ICG’s distribution into the fetus.