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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).

View larger version (17K): [in a new window]   Figure 1. Experimental perfusion protocols. White area = KHB, black area = KHB plus 0.5 mmol/L Gd-DTPA, gray area = KHB plus 0.5 mmol/L Gd-BOPTA, striped area = KHB plus 0.5 mmol/L Gd-BOPTA plus 0.5 mmol/L bromosulfophthlalein.

View larger version (112K): [in a new window]   Figure 2. A, B, Representative MR SI in a liver perfused with Gd-DTPA (A) and then with Gd-BOPTA (B) solutions. C, D, SI in a second liver perfused with Gd-DTPA (C) and Gd-BOPTA plus bromosulfophthalein (D) solutions. Transverse images were collected at baseline (1), during hepatic uptake (2-4), and during hepatic washout (5) and were obtained by using fast gradient-echo T1-weighted MR sequence preceded by a 90° saturation pulse with the following parameters: 6.8/3, flip angle of 90°, matrix of 256 x 256; one image per 8 seconds, field of view of 14 cm, and section thickness of 0.7 cm.

View larger version (35K): [in a new window]   Figure 3. Experimental time curves of hepatic SIs obtained during the perfusion of 0.5 mmol/L Gd-DTPA (), 0.5 mmol/L Gd-BOPTA (), 0.5 mmol/L Gd-BOPTA plus 0.5 mmol/L bromosulfophthalein (), and 0.5 mmol/L Gd-BOPTA in livers with acute bile duct ligation (). The combined perfusion of bromosulfophthalein and Gd-BOPTA decreases the SI enhancement in comparison with the perfusion of Gd-BOPTA alone.

View larger version (16K): [in a new window]   Figure 4. Half-lives (t1/2, in minutes) during the perfusion period (white bars) and the washout period (gray bars). DTPA = livers perfused with Gd-DTPA, BOPTA = livers perfused with Gd-BOPTA, BOPTA + BDL = livers isolated after acute bile duct ligation and perfused with KHB plus Gd-BOPTA, and BOPTA + BSP = livers perfused with Gd-BOPTA plus bromosulfophthalein. There were four livers in each group. The entry and exit kinetic parameters measured during the perfusion of Gd-BOPTA and bromosulfophthalein were comparable to those obtained during Gd-DTPA perfusion.

View larger version (27K): [in a new window]   Figure 5. Gadolinium concentrations in portal veins (), hepatic veins (), and hepatic tissues () during the 30-minute perfusion of Gd-BOPTA (three livers at each time point). In a similar protocol, livers were perfused with Gd-BOPTA plus bromosulfophthalein () (two livers at each time point) or Gd-DTPA () (two livers at each time point). When livers were perfused during 30 minutes with both bromosulfophthalein and Gd-BOPTA, the gadolinium concentration in hepatic tissues was similar to that measured in livers perfused with Gd-DTPA.