Rationale and objectives: To investigate the transport of the hepatobiliary magnetic resonance (MR) imaging contrast agent Gd-BOPTA into rat hepatocytes.
Materials and methods: In a MR-compatible hollow-fiber bioreactor containing hepatocytes, MR signal intensity was measured over time during the perfusion of Gd-BOPTA. For comparison, the perfusion of an extracellular contrast agent (Gd-DTPA) was also studied. A compartmental pharmacokinetic model was developed to describe dynamic signal intensity-time curves.
Results: The dynamic signal intensity-time curves of the hepatocyte hollow-fiber bioreactor during Gd-BOPTA perfusion were adequately fitted by 2 compartmental models. Modeling permitted to discriminate between the behaviors of the extracellular contrast agent (Gd-DTPA) and the hepatobiliary contrast agent (Gd-BOPTA). It allowed the successfully quantification of the parameters involved in such differences. Gd-BOPTA uptake was saturable at high substrate concentrations.
Conclusions: The transport of Gd-BOPTA into rat hepatocytes was successfully described by compartmental analysis of the signal intensity recorded over time and supported the hypothesis of a transporter-mediated uptake.