Evaluation of gadolinium-based contrast agents in juvenile CD-1 mice including behavioral evaluations.

Autor: Lewis EM; Charles River Laboratories, Inc., Safety Assessment, Horsham, Pennsylvania, USA., Jones P; GE Healthcare, Pharmaceutical Diagnostics, Chalfont St. Giles, UK., Clemens G; Bayer AG, Pharmaceuticals Research and Development, Berlin, Germany., Fretellier N; Guerbet, Roissy, France., Bussi S; Bracco Imaging SpA, Milan, Italy., Hirani E; GE Healthcare, Pharmaceutical Diagnostics, Chalfont St. Giles, UK., Czupalla O; Bayer AG, Pharmaceuticals Research and Development, Berlin, Germany., Tedoldi F; Bracco Imaging SpA, Milan, Italy., Bourrinet P; Guerbet, Roissy, France., Hoberman AM; Charles River Laboratories, Inc., Safety Assessment, Horsham, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Birth defects research [Birth Defects Res] 2024 Jan; Vol. 116 (1), pp. e2284. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1002/bdr2.2284
Abstrakt: Introduction: Seven gadolinium-based contrast agents (GBCAs), four linear and three macrocyclic, were evaluated for potential effects on development, including behavior of juvenile CD-1 mice.
Methods: The GBCAs were administered via intravenous injection once daily on postnatal day (PND) 9, 12, 15, 18, and 21 (PND 1 was the day of delivery) at doses up to twice the human equivalent clinical dose (i.e., 0.63 mmol Gd/kg for gadoxetate disodium and 2.5 mmol Gd/kg for the other GBCAs). Mice were bled for evaluation of exposure (plasma) to gadolinium (Gd) on PND 9, 12, and 70. At scheduled euthanasia, the liver, spleen, brain, skin (dorsal surface), bone (left femur), and kidneys were excised from up to six mice/sex/group on PND 10, 22, or 70 for the determination of Gd levels and histopathological analysis. All mice were monitored for toxicity, growth and survival, sexual maturation, and behavior.
Conclusion: Gd was quantifiable in the brain tissues with levels declining over time. There was no long-term effect on the growth and development for mice exposed to any of the GBCAs. There was no impact on neurodevelopment as assessed by brain histology and validated neurobehavioral tests, including a functional observational battery, motor activity, and learning and memory as evaluated in the Morris water maze. For all GBCAs, the highest dose tested represented the no-observable-adverse-effect level in juvenile mice.
(© 2023 Charles River Laboratories, Inc., Horsham, PA. Birth Defects Research published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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