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Title: 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];  [1]; ORCiD logo [1];  [1];  [1];  [2]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
  2. 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 Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1433132
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article: 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. doi: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. doi: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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