Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system.
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.
Schuhmann-Giampieri
G
G
Institute of Contrast Media Research, Schering AG Berlin/Bergkamen, Germany.
Schmitt-Willich
H
H
Press
W R
WR
Negishi
C
C
Weinmann
H J
HJ
Speck
U
U
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000033:anatomy & histology*; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity; D004341:Drug Evaluation; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008099:Liver / Q000033:anatomy & histology*; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D004369:Pentetic Acid / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D014018:Tissue Distribution
D003287:Contrast Media; D009942:Organometallic Compounds; C073590:gadolinium ethoxybenzyl DTPA; D004369:Pentetic Acid; D019786:Gadolinium DTPA