Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure

Abstract Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-ye...

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Autores principales:	Julie Davies, Michael Marino, Adrian P. L. Smith, Janell M. Crowder, Michael Larsen, Lisa Lowery, Jason Castle, Mark G. Hibberd, Paul M. Evans
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f519a8b0f8774562af658f799e688998
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spelling	oai:doaj.org-article:f519a8b0f8774562af658f799e6889982021-12-02T15:39:50ZRepeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure10.1038/s41598-021-93147-22045-2322https://doaj.org/article/f519a8b0f8774562af658f799e6889982021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93147-2https://doaj.org/toc/2045-2322Abstract Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-year after repeated gadodiamide dosing and tissue retention kinetics after a single administration. Histopathological and ultrastructural transmission electron microscopy (TEM) analysis revealed no findings in rats administered a cumulative dose of 12 mmol/kg. TEM-energy dispersive X-ray spectroscopy (TEM-EDS) localization of gadolinium in the deep cerebellar nuclei showed ~ 100 nm electron-dense foci in the basal lamina of the vasculature. Laser ablation-ICP-MS (LA-ICP-MS) showed diffuse gadolinium throughout the brain but concentrated in perivascular foci of the DCN and globus pallidus with no observable tissue injury or ultrastructural changes. A single dose of gadodiamide (0.6 mmol/kg) resulted in rapid cerebrospinal fluid (CSF) and blood clearance. Twenty-weeks post administration gadolinium concentrations in brain regions was reduced by 16–72-fold and in the kidney (210-fold), testes (194-fold) skin (44-fold), liver (42-fold), femur (6-fold) and lung (64-fold). Our findings suggest that gadolinium does not lead to histopathological or ultrastructural changes in the brain and demonstrate in detail the kinetics of a human equivalent dose over time in a pre-clinical model.Julie DaviesMichael MarinoAdrian P. L. SmithJanell M. CrowderMichael LarsenLisa LoweryJason CastleMark G. HibberdPaul M. EvansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julie Davies Michael Marino Adrian P. L. Smith Janell M. Crowder Michael Larsen Lisa Lowery Jason Castle Mark G. Hibberd Paul M. Evans Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
description	Abstract Gadolinium based contrast agents (GBCA) are used to image patients using magnetic resonance (MR) imaging. In recent years, there has been controversy around gadolinium retention after GBCA administration. We sought to evaluate the potential toxicity of gadolinium in the rat brain up to 1-year after repeated gadodiamide dosing and tissue retention kinetics after a single administration. Histopathological and ultrastructural transmission electron microscopy (TEM) analysis revealed no findings in rats administered a cumulative dose of 12 mmol/kg. TEM-energy dispersive X-ray spectroscopy (TEM-EDS) localization of gadolinium in the deep cerebellar nuclei showed ~ 100 nm electron-dense foci in the basal lamina of the vasculature. Laser ablation-ICP-MS (LA-ICP-MS) showed diffuse gadolinium throughout the brain but concentrated in perivascular foci of the DCN and globus pallidus with no observable tissue injury or ultrastructural changes. A single dose of gadodiamide (0.6 mmol/kg) resulted in rapid cerebrospinal fluid (CSF) and blood clearance. Twenty-weeks post administration gadolinium concentrations in brain regions was reduced by 16–72-fold and in the kidney (210-fold), testes (194-fold) skin (44-fold), liver (42-fold), femur (6-fold) and lung (64-fold). Our findings suggest that gadolinium does not lead to histopathological or ultrastructural changes in the brain and demonstrate in detail the kinetics of a human equivalent dose over time in a pre-clinical model.
format	article
author	Julie Davies Michael Marino Adrian P. L. Smith Janell M. Crowder Michael Larsen Lisa Lowery Jason Castle Mark G. Hibberd Paul M. Evans
author_facet	Julie Davies Michael Marino Adrian P. L. Smith Janell M. Crowder Michael Larsen Lisa Lowery Jason Castle Mark G. Hibberd Paul M. Evans
author_sort	Julie Davies
title	Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
title_short	Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
title_full	Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
title_fullStr	Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
title_full_unstemmed	Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
title_sort	repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f519a8b0f8774562af658f799e688998
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Repeat and single dose administration of gadodiamide to rats to investigate concentration and location of gadolinium and the cell ultrastructure

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