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. 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.
Highlights
The use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) has been ubiquitous in radiology for nearly three decades[1]
The respective efficacies of HOPO and diethylenetriaminepentaacetic acid (DTPA) as decorporation agents for the radiotracer 153Gd were probed in a murine model[8,10]
Intraperitoneal administration of both HOPO and DTPA was found to promote the clearance of 153Gd, and for both chelators, the extent of clearance varies with administration time relative to 153Gd contamination
Summary
The use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) has been ubiquitous in radiology for nearly three decades[1]. HOPO is an octadentate hydroxypyridinone ligand that is among the most competent chelating agents for heavy f-block metals (log KML at pH 7.4 for Gd of 20.5(1))[7] It is orally available, non-toxic at therapeutic dosages, and is extremely selective for actinide and lanthanide ions over biologically-relevant metal ions such as iron, potassium, and calcium[8]. Been approved for a first-in-human Phase 1 safety trial as an actinide decorporation agent[9] This led us to surmise that HOPO could provide an effective treatment for preventing and remediating the biological accumulation of Gd that has been observed in numerous recent studies. The respective efficacies of HOPO and DTPA as decorporation agents for the radiotracer 153Gd were probed in a murine model[8,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
