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

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Abstract

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.

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Abbreviations

IL-1:

interleukin-1

TNFα:

tumor necrosis factor alpha

INFγ:

interferon gamma

ROS:

reactive oxygen species

Pb:

lead

Cd:

cadmium

Hg:

mercury

Ni:

nickel

Al:

aluminum

GBCAs:

gadolinium-based contrast agents

NSF:

nephrogenic systemic fibrosis

DN:

dentate nucleus

GP:

globus pallidus

CSF:

cerebrospinal fluid

BBB:

blood-brain barrier

ATP:

adenosine triphosphate

LDH:

lactate dehydrogenase

MS:

multiple sclerosis

EDSS:

expanded disability status scale

ADC:

apparent diffusion coefficient

FDA:

Food and Drug Administration

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Acknowledgments

This paper is dedicated to the memory of our wonderful colleague, Dr. Marco Sarà, who recently passed away.

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Authors and Affiliations

  1. Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging and Interventional Radiology, Università Campus Bio-Medico di Roma, Rome, Italy

    Carlo A. Mallio & Carlo C. Quattrocchi

  2. Section of Neuroradiology, Department of Radiology, Autonomous University of Barcelona and Hospital Vall d’Hebron, Passeig Vall d’Hebron, Barcelona, Spain

    Àlex Rovira

  3. Department of Radiology, Antwerp University Hospital, Edegem, Belgium

    Paul M. Parizel

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  1. Carlo A. Mallio
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  2. Àlex Rovira
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  3. Paul M. Parizel
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  4. Carlo C. Quattrocchi
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Correspondence to Carlo A. Mallio.

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Mallio, C.A., Rovira, À., Parizel, P.M. et al. Exposure to gadolinium and neurotoxicity: current status of preclinical and clinical studies. Neuroradiology 62, 925–934 (2020). https://doi.org/10.1007/s00234-020-02434-8

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