Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents

Abstract

Ever since gadolinium was found to deposit in the brain of patients with normal kidney function by Kanda et al. in 2014, several studies have been conducted to evaluate its effect on the patients’ health. However, conflicting results were obtained regarding imaging in gadolinium retention. These finding were attributed to the chelating structure of the administered gadolinium-based contrast agent (GBCA): linear agents were found to accumulate in the dentate nucleus (DN) and the globus pallidus (GP) of subjects even after one dose. There are some contradictory results when assessing macrocyclic agents. In the following article, we review the basis of GBCAs characteristics and their side effects, as well as, the MRI studies that assessed the accumulation of gadolinium in the brain. Based on the results of several studies, in 2017, the European Medicine Agency requested the suspension of the marketing authorizations for three linear GBCAs: gadodiamide (Omniscan®), gadoversetamide (Optimark®) and gadopentate dimeglimine (Magnevist®) and limited the use of gadoxetate disodium (Primovist/Eovist®) and gadobenate dimeglumine (MultiHance®) to hepatic uptake for imaging poorly vascularized hepatic lesions. Accordingly, the FDA did not restrict GBCA use, but will continue to study their safety and urged clinicians to use these agents sparingly. All macrocyclic GBCAs continued however to be used as no available valid evidence linked them to brain gadolinium retention. Regardless of possible accumulation in the brain, there is no evidence to-date that gadolinium retention leads to any disease or disorders in subjects with normal renal function. Further investigations with long-term follow-up are needed.

Keywords:

• Gadolinium-based contrast agents
• linear
• macrocyclic
• MRI
• dentate nucleus
• globus pallidus

Acknowledgements

Lara Chehabeddine and Tala Al Saleh were involved in this research under the Medical Research Volunteer Program (MRVP) at the American University of Beirut.

Declaration of interest

There are no conflicts of interest associated with this publication and there has been no financial support for this work that could influence its outcome. The author’s affiliations are as shown on the cover page. The authors have sole responsibility for the writing and content of the paper. Preparation of this review was conducted during the normal course of the authors’ employment without any external support. The conduct of the review and the conclusions drawn represent the collective independent professional work of the authors and are not necessarily those of their employer or any sponsors.