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Radiology, Vol 183, 59-64, Copyright © 1992 by Radiological Society of North America

ARTICLES

Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system

G Schuhmann-Giampieri, H Schmitt-Willich, WR Press, C Negishi, HJ Weinmann and U Speck
Institute of Contrast Media Research, Schering AG Berlin/Bergkamen, Germany.

Gadolinium diethylenetriaminepentaacetic acid (DTPA) covalently linked to the lipophilic ethoxybenzyl moiety (Gd-EOB-DTPA) was designed for use as a contrast agent in hepatobiliary magnetic resonance imaging. With T1 relaxivity values of 8.7 L/mmol.second in plasma and 16.6 L/mmol.second in rat liver tissue and a median lethal dose of 10 mmol/kg when administered intravenously in mice and rats, Gd-EOB-DTPA has a fairly high margin of safety. In rats and monkeys, biodistribution studies performed 7 days after administration of 0.25 mmol/kg revealed very little retention of gadolinium (less than 1%) in the tissues, indicating complete elimination via renal and biliary excretion. Biliary excretion was inhibited by coadministration of sulfobromophthalein, indicating the involvement of a carrier-mediated transport system based on the enzyme glutathione-S-transferase. In rats, the biliary transport maximum was 5 mumol gadolinium/min.kg. High T1 relaxivity of Gd-EOB-DTPA in rat liver in vivo can be explained by transient interaction with intracellular components and by increased microviscosity inside the hepatocyte.


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