Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents
Abstract
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. Here, 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 153Gd 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.
- Authors:
-
[1];
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Nuclear Engineering
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1433132
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
Citation Formats
Rees, Julian A., Deblonde, Gauthier J. -P., An, Dahlia D., Ansoborlo, Camille, Gauny, Stacey S., and Abergel, Rebecca J. Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents. United States: N. p., 2018.
Web. doi:10.1038/s41598-018-22511-6.
Rees, Julian A., Deblonde, Gauthier J. -P., An, Dahlia D., Ansoborlo, Camille, Gauny, Stacey S., & Abergel, Rebecca J. Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents. United States. https://doi.org/10.1038/s41598-018-22511-6
Rees, Julian A., Deblonde, Gauthier J. -P., An, Dahlia D., Ansoborlo, Camille, Gauny, Stacey S., and Abergel, Rebecca J. Tue .
"Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents". United States. https://doi.org/10.1038/s41598-018-22511-6. https://www.osti.gov/servlets/purl/1433132.
@article{osti_1433132,
title = {Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents},
author = {Rees, Julian A. and Deblonde, Gauthier J. -P. and An, Dahlia D. and Ansoborlo, Camille and Gauny, Stacey S. and Abergel, Rebecca J.},
abstractNote = {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. Here, 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 153Gd 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.},
doi = {10.1038/s41598-018-22511-6},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {Tue Mar 13 00:00:00 EDT 2018},
month = {Tue Mar 13 00:00:00 EDT 2018}
}
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Primer on gadolinium chemistry
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Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms
journal, April 2016
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From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents
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Gadolinium toxicity: Iron and ferroportin as central targets
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Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of clinical experience
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A kinetic investigation of the lanthanide DOTA chelates. Stability and rates of formation and of dissociation of a macrocyclic gadolinium(III) polyaza polycarboxylic MRI contrast agent
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Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion
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Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent
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Nephrogenic Systemic Fibrosis: Suspected Causative Role of Gadodiamide Used for Contrast-Enhanced Magnetic Resonance Imaging
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Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy
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238 Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice
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