Gd-BOPTA transport into rat hepatocytes: pharmacokinetic analysis of dynamic magnetic resonance images using a hollow-fiber bioreactor

Invest Radiol. 2004 Aug;39(8):506-15. doi: 10.1097/01.rli.0000129156.16054.30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Bioreactors
  • Contrast Media / pharmacokinetics*
  • Gadolinium / pharmacokinetics
  • Gadolinium DTPA / pharmacokinetics
  • Hepatocytes / metabolism*
  • In Vitro Techniques
  • Magnetic Resonance Imaging*
  • Male
  • Meglumine / analogs & derivatives*
  • Meglumine / pharmacokinetics*
  • Membrane Transport Proteins / metabolism
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / metabolism
  • Organic Anion Transporters / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley


  • Contrast Media
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
  • Organometallic Compounds
  • gadobenic acid
  • Meglumine
  • Gadolinium
  • Gadolinium DTPA