A new lipophilic gadolinium chelate as a tissue‐specific contrast medium for MRI

Abstract

Gd-Ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a highly water-soluble paramagnetic contrast agent. Due to its protein binding of about 10% and its lipophilic residue, Gd-EOB-DTPA exhibits both renal (30% of the dose) and hepatobiliary (70%) excretion in rats. Despite its lipophilic character, the compound displays a low toxicity (LD50 = 7.5 mmol/kg). T1-relaxivity of 5.3 liters mmol-1 s-1 in water, 8.7 liters mmol-1 s-1 in plasma, and 16.9 liters mmol-1 s-1 in rat liver together with the hepatocellular uptake explain the liver-specific contrast enhancement of Gd-EOB-DTPA. The diagnostic dose is considerably lower than the amount of Magnevist used in abdominal imaging. The preclinical studies suggest its clinical role as being a hepatobiliary contrast agent for MRI.

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

“…Gd-EOB-DTPA with the hepatocyte-selective property is a recently developed contrast agent for hepatobiliary MR imaging (10,11). Previous studies have demonstrated that Gd-EOB-DTPA is well tolerated and has no substantial adverse events and minor adverse events of 5.9% (6,7,19).…”

“…On the other hand, the high T 1 relaxivity of Gd-EOB-DTPA is very important in the detection of hypervascular pathologies; therefore, the decreased dose of Gd-EOB-DTPA should be reassessed to avoid lower arterial enhancement. Preclinical studies have shown that Gd-EOB-DTPA is eliminated from the blood serum gradually, with complete excretion through the biliary and renal systems (10,13). Uptake of about 50% of injected Gd-EOB-DTPA is started by the anionic transporter protein of hepatocytes following contrast agent administration and leads to intracellular accumulation, and thus increased signal intensity of liver parenchyma on delayed T 1 -weighted MR images.…”

“…Gd-EOB-DTPA exhibits high hepatic uptake and high T 1 relaxivity in the liver, and shows peak enhancement effects in the normal liver at 20 minutes after injection on T 1 -weighted MR images (8 -12). Preclinical studies have shown that Gd-EOB-DTPA is eliminated through both the hepatobiliary and the renal systems (10,13). In addition to specific uptake by hepatocytes, Gd-EOB-DTPA allows for assessment of tumor perfusion during the vascular phase like Gd-DTPA (14).…”

Comparison between areas with Gd‐EOB‐DTPA uptake and without in hepatocellular carcinomas on Gd‐EOB‐DTPA‐enhanced hepatobiliary‐phase MR imaging: Pathological correlation

“…The uptake and elimination of gadoxetic acid are believed to require a higher level of hepatic function that involves the organic anion transport system such as the sodium-independent organic anion-transporting polypeptide (OATP1) and biliary drainage system by means of the adenosine triphosphate (ATP)-dependent canalicular multispecific organic anion transporter peptide (cMOAT), in which gadoxetic acid competes with bilirubin for the same organic anion excretory mechanisms (14)(15)(16)(17). It is known that positive contrast enhancement of HCCs on gadoxetic acid-enhanced hepatobiliary-phase images can be theoretically attributed to both active uptake of gadoxetic acid by HCCs with a residual hepatocytic function and impaired biliary excretion within the intratumoral region, as has been demonstrated in animal studies (12,15,18,19).…”

The emerging role of transport systems in liver function tests

“…Gadoxetate is excreted unaltered into rat bile (Weinmann et al, 1991) and its secretion into bile is almost completely blocked, when the animals are pretreated with BSP (de Haen et al, 1995). Rat Oat1a1, but not Oat1a4 or OATP1A2 (table 1), were found to transport gadoxetate .…”