Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents

The mechanisms were investigated for the hepatic transport of 4 different g adolinium complexes used as contrast agents for magnetic resonance imaging (MRI). In basolateral rat hepatocyte plasma membrane vesicles, Gd-DTPA upta ke was indistinguishable from non-specific binding to vesicles; Gd-BOPTA an d Gd-EOB-DTPA entered plasma membrane vesicles following a linear, concentr ation-dependent mechanism up to 1.5 mM of substrate. By contrast, Gd-B 2079 0 uptake followed a saturative kinetic with an apparent K-m of 92 +/- 15 mu M and a V-max of 143 +/- 42 pmol/mg prot/15 sec, and it occurred into an o smotic-sensitive space. Sulfobromophthalein ant taurocholate, but not uncon jugated bilirubin inhibited the uptake rate of Gd-B 20790 but not that of t he other three compounds, Injection into Xenopus laevis oocytes of 5 ng of human OATP cRNA resulted, after 3 days, in a greater than or equal to 2-fol d stimulation (p < 0.001) of transport of Gd-B 20790 but not of Gd-BOPTA or Gd-EOB-DTPA. Collectively, these data indicate that the hepatic uptake of the MRI contrast agent Gd-B 20790 is a carrier-mediated mechanism operated by OATP while MRI compounds with other chemical structures enter the hepato cyte by other mechanisms. (C) 1999 Academic Press.