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Abstract: SA-PO934

Confounded Magnetic Resonance Imaging Contrast Agent Exposures and Gadolinium Retention in Organs

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine

Authors

  • Dokladny, Karol, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Deaguero, Joshua, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Ali, Abdul Mehdi S., University of New Mexico, Albuquerque, New Mexico, United States
  • Henderson, Ian, Kidney Institute of New Mexico, Albuquerque, New Mexico, United States
  • Degnan, James H., University of New Mexico, Albuquerque, New Mexico, United States
  • Escobar, G. Patricia, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Wagner, Brent, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Background

In 2006, gadolinium-based contrast agents (GBCAs) were linked to nephrogenic systemic fibrosis, a rare but highly disabling and often fatal condition. GBCAs can also induce kidney injury and fatal encephalopathy. The US Food and Drug Administration ordered a black box warning for all gadolinium-based contrast agents. There are two general classes of GBCAs: linear (e.g., Omniscan) and macrocyclic (Dotarem). Our previous research indicated that prior GBCA exposures influence gadolinium retention in the kidney or liver. The present study aimed to test whether a similar paradigm holds for other vital organs.

Methods

18 male mice were randomized to five experimental groups: (1) saline-treated controls; gadolinium-based contrast agent-treated (2) Omniscan (OMN), (3) Dotarem (DOT), or in combination (4) OMN (1 week) followed by DOT administration for 3 weeks or (5) DOT (1 week) followed by OMN treatment for 3 weeks. Per our established protocols, saline or contrast agents were administered via intraperitoneal injections 5 days a week for 4 weeks. Lung, heart, adipose tissue, and skeletal muscle tissue were excised and snap-frozen in liquid nitrogen. On average, 15 mg of tissue were digested in nitric acid, and gadolinium concentrations were quantified using PerkinElmer NexION 5000 inductively coupled plasma mass spectrometry (ICP/MS) with a detection limit of 0.01 ppb.

Results

A 4-week treatment of OMN or DOT alone or in combination (OMN-DOT or DOT-OMN) resulted in a significant accumulation of gadolinium in the lung and heart. Gadolinium deposition was equal for Omniscan, OMN-DOT, and DOT-OMN. No differences existed among any group for Zn or P, regardless of the organ.

Conclusion

Gadolinium is retained in the heart and lung for linear, macrocyclic, and confounded agent exposure. Adipose retains macrocyclic agents. Skeletal muscle retains linear agents. Our study is underpowered with respect to the other experimental groups for adipose and skeletal muscle. Future studies are required to determine those tissue-specific differences.