Isolated Perfused Rat Livers to Quantify the Pharmacokinetics and Concentrations of Gd-BOPTA

Figure 1

Gd-BOPTA transport across hepatocyte membranes. The MRI contrast agent distributes into sinusoids and interstitium before entry into rat hepatocytes across the organic anion transporting polypeptides (Oatp1a1/a4/b2). Once inside hepatocytes, Gd-BOPTA exits into bile canaliculi (BC) across the multiple resistance-associated protein 2 (Mrp2) or back into sinusoids across the sinusoidal membrane. Gd-BOPTA liver concentrations are estimated by liver MRI or quantified with a gamma counter when the molecule is labelled with ¹⁵³Gd. Sinusoidal clearance to liver (_SINCL_LIVER, ml/min) is [(C_PV–C_HV) × 30]/C_PV, where C_PV is the concentration (µM) in portal vein and 30 ml/min is the constant liver flow rates. The clearance from hepatocytes to bile canaliculi (_HCCL_BC, ml/min) is (C_BC × bile flow rates)/C_HC, where C_BC is the Gd-BOPTA concentration in bile canaliculi and C_HC is the Gd-BOPTA concentration in hepatocytes. The clearance from hepatocytes to interstitium (_HCCL_INT, ml/min) is (C_HV × 30)/C_HC, where C_HV is the Gd-BOPTA concentration in the hepatic veins. The Gd-BOPTA concentrations (illustrated by the number of circles) increase from sinusoids, to hepatocytes, and to bile canaliculi.