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Gadolinium Tissue Distribution in a Large-Animal Model after a Single Dose of Gadolinium-based Contrast Agents
Henning Richter1, Patrick Bücker1, Louise Françoise Martin1
1From the Diagnostic Imaging Research Unit, Clinic for Diagnostic Imaging, Department of Clinical Diagnostics and Services (H.R.), Clinic for Zoo Animals, Exotic Pets and Wildlife (L.F.M.), and Musculoskeletal Research Unit, Department of Molecular Mechanisms of Disease (A.K.), Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 258c, 8057 Zurich, Switzerland; Clinic for Neuroradiology, University Hospital Bonn, Bonn, Germany (H.R., A.R.); Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany (P.B., C.D., S.F., M.S., U.K.); Clinical Neuroimaging, German Center for Neurodegenerative Diseases, Bonn, Germany (A.R.); and Institute of Neuropathology, University Hospital Münster, Münster, Germany (A.X., A.J.).
Abstract:
Background There is an ongoing scientific debate about the degree and clinical importance of gadolinium deposition in the brain and other organs after administration of gadolinium-based contrast agents (GBCAs). While most published data focus on gadolinium deposition in the brain, other organs are rarely investigated. Purpose To compare gadolinium tissue concentrations in various organs 10 weeks after one injection (comparable to a clinically applied dose) of linear and macrocyclic GBCAs in a large-animal model. Materials and Methods In this prospective animal study conducted from March to May 2018, 36 female Swiss-Alpine sheep (age range, 4-10 years) received one injection (0.1 mmol/kg) of macrocyclic GBCAs (gadobutrol, gadoteridol, and gadoterate meglumine), linear GBCAs (gadodiamide and gadobenate dimeglumine), or saline. Ten weeks after injection, sheep were sacrificed and tissues were harvested. Gadolinium concentrations were quantified with inductively coupled plasma mass spectrometry (ICP-MS). Histologic staining was performed. Data were analyzed with nonparametric tests. Results At 10 weeks after injection, linear GBCAs resulted in highest mean gadolinium concentrations in the kidney (502 ng/g [95% CI: 270, 734]) and liver (445 ng/g [95% CI: 202, 687]), while low concentrations were found in the deep cerebellar nuclei (DCN) (30 ng/g [95% CI: 20, 41]). Tissue concentrations of linear GBCAs were three to 21 times higher compared with those of macrocyclic GBCAs. Administered macrocyclic GBCAs resulted in mean gadolinium concentrations of 86 ng/g (95% CI: 31, 141) (P = .08) in the kidney, 21 ng/g (95% CI: 4, 39) (P = .15) in liver tissue, and 10 ng/g (95% CI: 9, 12) (P > .99) in the DCN, which were not significantly elevated when compared with concentrations in control animals. No histopathologic alterations were observed irrespective of tissue concentrations within any examined organ. Conclusion Ten weeks after one injection of a clinically relevant dose of gadolinium-based contrast agents, the liver and kidney appeared to be reservoirs of gadolinium; however, despite gadolinium presence, no tissue injury was detected. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Clément in this issue.
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