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Abstract: SA-PO264

Magnetic Resonance Imaging Contrast Agent Safety: Prodigious Phosphorus in Renal Gadolinium-Rich Nanoparticles

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Wagner, Brent, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Dokladny, Karol, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Escobar, G. Patricia, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Deaguero, Joshua, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Henderson, Ian, Omphalos Bioscience, Albuquerque, New Mexico, United States
  • Howard, Tamara A., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Brearley, Adrian, University of New Mexico, Albuquerque, New Mexico, United States
Background

Magnetic resonance imaging (MRI) contrast agent complications include fibrosis, kidney injury, and fatal gadolinium encephalopathy. Routine diagnostic imaging leads to the formation of gadolinium-rich nanoparticles in human kidneys. The mechanism is unclear.

Methods

Mice were treated with a MRI contrast agent. After four weeks of treatment and a washout period of 0.5 weeks, the kidneys were harvested. Flash-frozen kidney samples were homogenized in radioimmunoprecipitation assay buffer. Gadolinium-rich nanoparticles were purified from homogenate ultracentrifuged through sucrose gradients of different concentrations. We localized the nanoparticles using transmission electron microscopy (TEM). The elemental characterization of the nanoparticles was obtained using X-ray energy-dispersive spectroscopy (aberration-corrected scanning TEM, JEOL NEOARM). We compared quantities between core and coronal areas using a two-tailed t-test. We adjusted the p-values using the Benjamini-Hochberg (B-H) method to account for false discoveries.

Results

Electron-dense intracellular debris peppered the proximal tubular epithelium. The dendritic cores and coronas contained high levels of gadolinium. Among the elements, phosphorus was 9.5-fold higher in the cores (p = 1.2 × 106).

Conclusion

There is more than one side to the argument concerning the safety of MRI contrast agents. Our findings suggest that nanoparticulate dendritic cores exhibit high phosphorus levels, which does not support the formation of GdPO4 precipitate. These results contribute to understanding the mechanism of gadolinium-induced complications.

The elemental composition of intracellular gadolinium-rich nanoparticulate cores is glutted in phosphorus than the peripheral coronas.

Funding

  • NIDDK Support