Abstract: TH-PO092
Detecting the Metabolism of Gadolinium-Based Contrast Agents Using Electron Paramagnetic Resonance (EPR) Spectroscopy
Session Information
- AKI: Mechanisms - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wagner, Brent, New Mexico VA Health Care System, Albuquerque, New Mexico, United States
- Hong, Emily, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
- Yang, Jing, University of New Mexico Department of Chemistry and Chemical Biology, Albuquerque, New Mexico, United States
- Dokladny, Karol, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
- Deaguero, Joshua, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
- Escobar, G. Patricia, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
Group or Team Name
- Kidney Institute of New Mexico
Background
Magnetic resonance imaging (MRI) contrast agents cause kidney injury, symptoms associated with gadolinium (Gd) exposure (SAGE), and 'nephrogenic' systemic fibrosis. Contrast agents are mutlidentate complexes designed to chelate Gd to 1) reduce free ion toxicity and 2) enhance renal elimination. Whether liberation of Gd from these complexes is a mechanistic step of disease has yet to be proven.
Methods
Mice were administered MRI contrast agent as per routine in our laboratory. Room temperature solution EPR spectroscopy was performed using a Bruker EMX spectromert with associated Bruker magnetic control electronics and microwave bridges. The microwave frequency was ∼9.4 GHz, field attenuation 20-25 dB, modulation amplitudes 6 - 10G, 3.17×105 gain, and up to 16 scans.
Results
The g values for Dotarem (macocylic) and Omniscan (open-chained) were 1.9791 ± 0.0025 (mean, S.D.) and 1.9374 ± 0.0040, respectively.The g values for Omniscan and Dotarem did not change significantly regardless of freezing/thawing. Concentrated HCl altered the EPR spectra of gadolnium-based contrast agent regardless of class. The EPR spectra remained unchanged in mouse urine days after last administration.
Conclusion
The healthcare system largely disinherits individuals with gadolinium-induced complications, many of whom seek off-label therapies such as metal chelation. The affinities of proprietary chelates for gadolinium will not govern equilibrium (chelate-bound metal) as gadolinium precipitates into insoluble minerals according to Le Chatelier's principle. These discoveries provide the foundation for developing rational therapies and improving the safety of magnetic resonance imaging contrast agents.
EPR spectra of Dotarem and urine from a single gadolinium-treated mouse.
Funding
- NIDDK Support