Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats.
OBJECTIVE
Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI.


METHODS
Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel.


RESULTS
In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second.


CONCLUSIONS
Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions.
Clément
O
O
Department of Radiology, University of California San Francisco 94143-0628.
Mühler
A
A
Vexler
V
V
Berthezène
Y
Y
Brasch
R C
RC
D000818:Animals; D002779:Cholestasis / Q000175:diagnosis* / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D019786:Gadolinium DTPA; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008657:Metabolic Clearance Rate; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D009942:Organometallic Compounds; C073590:gadolinium ethoxybenzyl DTPA; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA