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Kinetics of Gadobenate Dimeglumine in Isolated Perfused Rat Liver: MR Imaging Evaluation¹

¹ From the Department of Radiology, Hôpital Universitaire de Genève, Rue Micheli-du-Crest 24, Bâtiment C, Room 6-795, 1211 Geneva 14, Switzerland (C.M.P., X.M., F.T., J.P.V.), Pharmacy Section, Université de Lausanne, Switzerland (C.P., J.M.); Bracco Research, Geneva, Switzerland (S.P.); and Bracco Research, Milan, Italy (V.L.). Received June 10, 2002; revision requested August 20; final revision received November 26; accepted January 28, 2003. C.M.P. supported by Fond National Suisse de la Recherche Scientifique grants 3200-063619.00 and 3200-100868. Address correspondence to C.M.P. (e-mail: catherine.pastor@hcuge.ch).

PURPOSE: 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.

MATERIALS AND 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.

CONCLUSION: In the liver, the hepatospecific contrast agent Gd-BOPTA enters into hepatocytes likely through the organic anion transporting peptide 1.

© RSNA, 2003

Index terms: Animals • Contrast media, experimental studies • Experimental study • Gadolinium • Liver, MR, 76.121412, 76.121416, 76.12143 • Magnetic resonance (MR), contrast media, 76.12143 • Radiobiology, cell and tissue studies

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