Kinetics of gadobenate dimeglumine in isolated perfused rat liver: MR imaging evaluation.
OBJECTIVE
To compare in the entire liver, the hepatic kinetics of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) and to evaluate the hepatic transport of Gd-BOPTA.


METHODS
The authors studied both contrast agents in isolated perfused rat livers by measuring the magnetic resonance (MR) signal intensity (SI) in 12 rats, as well as the gadolinium concentrations in hepatic tissues in 42 rats. The intrahepatic transport of Gd-BOPTA was investigated with pharmacologic antagonism by using bromosulfophthalein. MR imaging was performed at 1.5 T with a fast gradient-echo T1-weighted MR sequence.


RESULTS
The hepatic kinetics based on the MR SI measured over time showed a rapid steady state during Gd-DTPA perfusion, while the SI continuously increased during the 30-minute Gd-BOPTA perfusion period. The pharmacokinetic modeling indicated that the half-lives of Gd-DTPA entry and exit were identical (mean, 1.3 minutes +/- 0.9 [standard error of mean]) and shorter than those observed with Gd-BOPTA (P <.001). The uptake of Gd-BOPTA was faster (mean half-life, 4.8 minutes +/- 0.3) than the washout (mean half-life, 17.5 minutes +/- 2.8) (P =.001). The combined perfusion of bromosulfophthalein and Gd-BOPTA decreased the SI enhancement in comparison with the perfusion of Gd-BOPTA alone (mean, 0.56 +/- 0.03 vs 2.54 +/- 0.39, P <.001). The entry and exit kinetic parameters obtained during the perfusion of Gd-BOPTA plus bromosulfophthalein were identical and comparable to those obtained during Gd-DTPA perfusion (P =.95). Acute bile duct ligation did not interfere with the uptake of Gd-BOPTA in hepatocytes, but it slowed down the excretion by approximately 50%. Measurements of gadolinium concentrations in hepatic tissues confirmed these findings.


CONCLUSIONS
In the liver, the hepatospecific contrast agent Gd-BOPTA enters into hepatocytes likely through the organic anion transporting peptide 1.
Pastor
Catherine M
CM
Department of Radiology, Hôpital Universitaire de Genève, Rue Micheli-du-Crest 24, Bâtiment C, Room 6-795, 1211 Geneva 14, Switzerland. catherine.pastor@hcuge.ch
Planchamp
Corinne
C
Pochon
Sibylle
S
Lorusso
Vito
V
Montet
Xavier
X
Mayer
Joachim
J
Terrier
Francois
F
Vallee
Jean-Paul
JP
D000818:Animals; D001692:Biological Transport; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000494:pharmacology; D005682:Gadolinium / Q000493:pharmacokinetics* / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000493:pharmacokinetics / Q000494:pharmacology
D003287:Contrast Media; D009942:Organometallic Compounds; D013448:Sulfobromophthalein; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium; D019786:Gadolinium DTPA