Evaluating the Effect of Sorafenib on Gd-EOB-DTPA-mediated Contrast Enhancement: An Experimental Study using DCE-MRI

Despite the potential impact of sorafenib on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-mediated contrast enhancements, attempts to assess these effects are rare. This study aimed to investigate the interaction between Sorafenib and Gd-EOB-DTPA by quantifying the T1 and T2 relaxation times and the relative enhancement rates (RERs) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the liver.

The effects on contrast enhancement were assessed using MRI with Chang liver cells and SD rats. MR phantom images were obtained after treating cells with varying dosages of Gd-EOB-DTPA (5, 10 mM) and sorafenib (10, 30 μM) to evaluate MR relaxivities. For the animal study, DCE-MRI was performed following intravenous administration of 25 µmol/kg Gd-EOB-DTPA and two different doses of sorafenib (10, 30 mg/kg). RER was analyzed to evaluate sorafenib's effects on Gd-EOB-DTPA uptake in the liver.

Phantom experiments demonstrated alterations in T1 and T2 values, with a tendency towards shortening disrupted by the addition of sorafenib to Gd-EOB-DTPA-treated Chang liver cells. The RERs of DCE-MRI in the liver exhibited a dose-dependent decrease following sorafenib administration, with recovery observed after 4 h.

Our results provide quantitative information on sorafenib-mediated interference with Gd-EOB-DTPA-induced contrast enhancement and offer experimental evidence suggesting the possibility of drug-drug interactions between sorafenib and Gd-EOB-DTPA. Although further research is needed to fully elucidate the impact of these interactions, caution is warranted when using these two agents concurrently for liver MRI.