Gadolinium Deposition in the Rat Brain after Repeated Administration of the Liver-Specific Gadolinium-Based Contrast Agent Gadoxetic Acid.

Abstract

Background: Studies on gadolinium deposition have recently been reported.

Objective: The objective of this study was to investigate whether there is an increased magnetic resonance signal intensity (SI) of the dentate nucleus (DCN) and quantification of gadolinium (Gd) brain concentrations by inductively coupled plasma-mass spectrometry (ICP-MS) test in rats who had undergone multiple administrations of gadoxetic acid and gadobutrol.

Materials and methods: Sprague-Dawley rats (24) were equally divided into three groups. Eight animals per group received 20 intravenous injections of gadoxetic acid (0.15 mmol/kg) and gadobutrol (0.6 mmol/kg) per injection. MRI was performed at 0, 5, and 20 weeks. Subsequently, all animals were euthanized and their brains were dissected for Gd quantification by ICP-MS.

Results: ICP-MS revealed higher Gd content in cerebellum tissue after administration of gadoxetic acid compared to gadobutrol (P < 0.05). The mean Gd concentrations in the cerebellum were 0.48 nmol/g gadoxetic acid and 0.26 nmol/g gadobutrol after intravenous administration. No visually evident enhancement was found after administration of gadoxetic acid, gadobutrol, or saline at any time point. The DCN-to-pons SI ratios for gadoxetic acid and gadobutrol were not different from the saline control group (P > 0.05, saline vs. gadoxetic acid and saline vs. gadobutrol, respectively).

Conclusions: Our results demonstrated that gadolinium concentrations in the cerebellum after intravenous gadoxetic acid administration were higher than for gadobutrol. Multiple administrations of gadoxetic acid disodium are not associated with increased SI in DCN.