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Precipitation of gadolinium from magnetic resonance imaging contrast agents may be the Brass tacks of toxicity

Journal Article · · Magnetic Resonance Imaging
 [1];  [2];  [2];  [3];  [4];  [2];  [2];  [2];  [2];  [1]
  1. Univ. of New Mexico, Albuquerque, NM (United States); New Mexico VA Health Care System, Albuquerque, NM (United States)
  2. Univ. of New Mexico, Albuquerque, NM (United States)
  3. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  4. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
+ Show Author Affiliations

The formation of gadolinium-rich nanoparticles in multiple tissues from intravenous magnetic resonance imaging contrast agents may be the initial step in rare earth metallosis. The mechanism of gadolinium-induced diseases is poorly understood, as is how these characteristic nanoparticles are formed. Gadolinium deposition has been observed with all magnetic resonance imaging contrast agent brands. Aside from endogenous metals and acidic conditions, little attention has been paid to the role of the biological milieu in the degradation of magnetic resonance imaging contrast agents into nanoparticles. Herein, we describe the decomposition of the commercial magnetic resonance imaging contrast agents Omniscan and Dotarem in the presence of oxalic acid, a well-known endogenous compound. Omniscan dechelated rapidly and preluded measurement by the means available, while Dotarem underwent a two-step decomposition process. The decomposition of both magnetic resonance imaging contrast agents by oxalic acid formed gadolinium oxalate (Gd2[C2O4]3, Gd2Ox3). Furthermore, both observed steps of the Dotarem reaction involved the associative addition of oxalic acid. Adding protein (bovine serum albumin) increased the rate of dechelation. Displacement reactions could occur at lysosomal pH. Through these studies, we have demonstrated that magnetic resonance imaging contrast agents can be dissociated by endogenous molecules, thus illustrating a metric by which gadolinium-based contrast agents (GBCAs) might be destabilized in vivo.

Research Organization:
Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); United States Department of Veterans Affairs; National Institutes of Health (NIH); University of New Mexico (UNM)
Grant/Contract Number:
NA0003525; 89233218CNA000001
OSTI ID:
2584370
Journal Information:
Magnetic Resonance Imaging, Journal Name: Magnetic Resonance Imaging Vol. 119; ISSN 0730-725X
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

Gadodiamide
Gadolinium
Gadoterate
MRI contrast agents
Metal complex
Metallosis
Oxalate
Stability
Systemic fibrosis