Gadolinium-ethoxybenzyl–DTPA, a new liver-directed magnetic resonance contrast agent: Absence of acute hepatotoxic, cardiovascular, or immunogenic effects

Rationale and Objectives: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB–DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB–DTPA injection have been limited. Methods: The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB–DTPA using detection of specific antibodies. Results: Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB–DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3—0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB–DTPA in the intact rat. Conclusions: The results further support preliminary conclusions that Gd–EOB–DTPA is a well-tolerated MR contrast agent.