Gd-BOPTA transport into rat hepatocytes: pharmacokinetic analysis of dynamic magnetic resonance images using a hollow-fiber bioreactor.
OBJECTIVE
To investigate the transport of the hepatobiliary magnetic resonance (MR) imaging contrast agent Gd-BOPTA into rat hepatocytes.


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.
Planchamp
Corinne
C
Geneva University Hospitals, Radiology Department, Geneva, Switzerland. corinne.planchamp@hcuge.ch
Gex-Fabry
Marianne
M
Dornier
Christophe
C
Quadri
Rafael
R
Reist
Marianne
M
Ivancevic
Marko K
MK
Vallée
Jean-Paul
JP
Pochon
Sibylle
S
Terrier
François
F
Balant
Luc
L
Stieger
Bruno
B
Meier
Peter J
PJ
Pastor
Catherine M
CM
D000818:Animals; D001692:Biological Transport; D019149:Bioreactors; D003287:Contrast Media / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000378:metabolism*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D026901:Membrane Transport Proteins / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D005682:Gadolinium; D019786:Gadolinium DTPA; D008536:Meglumine; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D009942:Organometallic Compounds; C064572:gadobenic acid