The Safety of Magnetic Resonance Imaging Contrast Agents (Aug 2024).

Article link: https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2024.1376587/full

Journal: Frontiers in Toxicology

Authors and Affiliations: Amy Cunningham 1, Martin Kirk 2, Emily Hong 1, Jing Yang 2, Tamara Howard 3, Adrian Brearley 4, Angelica Sáenz-Trevizo 4, Jacob Krawchuck 5, John Watt 6, Ian Henderson 7, Karol Dokladny 8, Joshua DeAguero 8, G Patricia Escobar 8, Brent Wagner 8 ,9

• 1School of Medicine, University of New Mexico Health Science Center, Albuquerque, NM, United States.

• 2Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM, United States.

• 3Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM, United States.

• 4Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM, United States.

• 5Sandia National Laboratory, Center for Integrated Nanotechnologies, Albuquerque, NM, United States.

• 6Los Alamos National Laboratory, Center for Integrated Nanotechnologies, Albuquerque, NM, United States.

• 7Omphalos Bioscience, Albuquerque, NM, United States.

• 8Kidney Institute of New Mexico, University of New Mexico Health Science Center, Kidney Institute of New Mexico, Albuquerque, NM, United States.

• 9New Mexico VA Healthcare System, Research Service, Albuquerque, NM, United States.

Abstract: “Gadolinium-based contrasts (GBCAs) are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models”.

“Therefore, physiologic conditions substantially modify the chemical equilibration, lending to the dissociation of gadolinium from the ligand (Eq. 3). In the presence of intracellular gadolinium-rich deposits, gadolinium continues to dissociate from the proprietary chelates. Because the dissociated gadolinium is trapped in insoluble nanoparticles, gadolinium is effectively out-of-play for a reverse reaction (i.e., Gd(κ7-L)(H2O)). This application of Le Châtelier’s principle, combined with the modified equilibrium due to an in vivo environment, means that gadolinium will disassociate from the pharmaceutical contrast no matter the brand of contrast agent (regardless of the log(Keq)). Intracellular rare earth metallic nanoparticles indisputably disrupt cellular harmonics. The ability of gadolinium to de-chelate has significant implications for current diagnostic practices and initial and repeated exposures. Intracellular, intraneuronal gadolinium-laden debris should not be subject to elimination by chelates relegated to the extracellular space”.

“The degradation of magnetic resonance imaging contrast agents into gadolinium-rich nanoparticles may be the initial step in complications and chronic disease. The nanoparticulate form of gadolinium differs from the base element gadolinium. Several experimental effects of magnetic resonance imaging contrast agent-induced gadolinium-rich nanoparticles include reactive oxygen species generation, oxidative stress (Wagner et al., 2012; Drel et al., 2016; Wagner et al., 2016; Bruno et al., 2021), mitochondrial perturbation (DeAguero et al., 2023), tissue infiltration with inflammatory cells (Wagner et al., 2012; Drel et al., 2016; Wagner et al., 2016; Do et al., 2019a; Do et al., 2019b; Do et al., 2022), and uptake in brain neurons (McDonald et al., 2017; Stanescu et al., 2020; Davies et al., 2021). Our data makes us suspect that the nanoparticles are forming within the cells.”

“As previously reviewed, both linear and macrocyclic agents were found in post-mortem human brain specimens from patients with normal renal function. However, concentrations of deposited macrocyclic agents were comparatively lower than with linear agents (Ramalho et al., 2017). The implications of harboring potentially toxic nanoparticles in organs such as the brain have yet to be thoroughly studied”.

“Disinherited by the medical establishment, patients spend an eternal time in chronic symptomatic purgatory. Escaping complications from a gadolinium administration is not a sign of providence. It indicates that there are undiscovered factors.”

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