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Abstract #0511

Gadolinium Deposition in the brain: Pre-clinical Investigation of differences in concentration, Distribution and histology in animals after repeated Administrations of linear and macrocyclic GBCAs

Hubertus Pietsch1, Thomas Frenzel1, Anna-Lena Frisk1, Diana Constanze Lenhard2, Gregor Jost1, Martin Andrew Sieber1, Astrid Zimmermann3, Volker Nischwitz3, and Jessica Lohrke1

1Bayer Healthcare, Berlin, Germany, 2Charité, Humboldt University Berlin, Berlin, Germany, 3Forschungszentrum Jülich, Jülich, Germany

Recent publications reported increased T1-weighted signal intensities in the dentate nucleus of patients who received multiple contrast-enhanced MRI scans. In this animal study histopathological changes and gadolinium retention in the skin and brain of rats after twenty intravenous injections of linear and macrocyclic GBCAs at high doses (2.5mmol/kgbw) were systematically investigated. The Gd brain concentrations of linear GBCAs (gadodiamide, gadopentetate dimeglumine) were significantly higher than those of macrocyclic agents (gadobutrol, gadoteridol). Since no morphological changes could be detected by routine H&E microscopic examination, immunohistochemistry and special stains, these findings are considered be of no toxicological relevance in rats.

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