Exposure to gadolinium and neurotoxicity: current status of preclinical and clinical studies

Purpose: Gadolinium is a rare-earth lanthanide metal that is known to have a direct neurotoxic effect. The scope of the present review is to summarize the current preclinical and clinical evidence on the association between exposure to gadolinium of the central nervous system and neurotoxicity. Methods: A literature review was performed by searching for original research papers investigating on gadolinium exposure and neurotoxicity. Results: Gadolinium is neurotoxic through multiple mechanisms, mainly involving Ca++ homeostasis and mitochondrial functions, as shown by preclinical in vitro studies. The available evidence related to the four different classes of gadolinium-based contrast agents commonly applied in clinical practice (i.e., linear and macrocyclic based on ligand structure, and ionic and non-ionic based on their net molecular charge) suggests that serial intravenous injections of gadolinium-based contrast agents and gadolinium brain depositions are not associated to histological changes, as confirmed by preclinical animal and human (MR imaging and autopsy) studies. Conclusion: To date, no cause-effect relationship has been demonstrated in patients between brain gadolinium exposure and clinical consequences specific to neurological toxicity. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.