Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-ba...

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Bibliographic Details
Published in:Scientific reports 2018-03, Vol.8 (1), p.4419-9, Article 4419
Main Authors: Rees, Julian A., Deblonde, Gauthier J.-P., An, Dahlia D., Ansoborlo, Camille, Gauny, Stacey S., Abergel, Rebecca J.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
631/1647/245/1628
631/45/49
64/60
692/308/153
Animals
BASIC BIOLOGICAL SCIENCES
Chelating Agents - therapeutic use
Chelation
Chelation Therapy - methods
Contrast agents
Contrast Media
Disease Models, Animal
Gadolinium
Gadolinium - adverse effects
Gadolinium - chemistry
Gadolinium - metabolism
Gadopentetate dimeglumine
Heavy metals
Humanities and Social Sciences
Humans
Magnetic Resonance Imaging
Metabolic Diseases - diagnostic imaging
Metabolic Diseases - drug therapy
Metabolic Diseases - etiology
Metabolic Diseases - metabolism
Mice
multidisciplinary
Radioactive tracers
Science
Science (multidisciplinary)
Speciation
Therapeutic applications
Treatment Outcome
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Summary:Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. To address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, a ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153 Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-22511-6