An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator

Abstract Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provid...

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Autores principales:	Patrick Werner, Matthias Taupitz, Leif Schröder, Patrick Schuenke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/34db663745f048b2b7583c090fc8cf5c
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spelling	oai:doaj.org-article:34db663745f048b2b7583c090fc8cf5c2021-11-08T10:55:35ZAn NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator10.1038/s41598-021-00974-42045-2322https://doaj.org/article/34db663745f048b2b7583c090fc8cf5c2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00974-4https://doaj.org/toc/2045-2322Abstract Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provide critical insights into kinetics and thermodynamic equilibria of underlying processes, which give hints towards the in vivo situation. We developed a time-resolved MRI relaxometry-based approach that exploits distinct relaxivities of Gd3+ in different molecular environments. Its applicability to quantify the transmetallation of GBCAs, the binding of Gd3+ to competing chelators, and the combined transchelation process is demonstrated. Exemplarily, the approach is applied to investigate two representative GBCAs in the presence of Zn2+ and heparin, which is used as a model for a macromolecular and physiologically occurring chelator. Opposing indirect impacts of heparin on increasing the kinetic stability but reducing the thermodynamic stability of GBCAs are observed. The relaxivity of resulting Gd-heparin complexes is shown to be essentially increased compared to that of the parent GBCAs so that they might be one explanation for observed long-term MRI signal enhancement in vivo. In forthcoming studies, the presented method could help to identify the most potent Gd-complexing macromolecular species.Patrick WernerMatthias TaupitzLeif SchröderPatrick SchuenkeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrick Werner Matthias Taupitz Leif Schröder Patrick Schuenke An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
description	Abstract Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provide critical insights into kinetics and thermodynamic equilibria of underlying processes, which give hints towards the in vivo situation. We developed a time-resolved MRI relaxometry-based approach that exploits distinct relaxivities of Gd3+ in different molecular environments. Its applicability to quantify the transmetallation of GBCAs, the binding of Gd3+ to competing chelators, and the combined transchelation process is demonstrated. Exemplarily, the approach is applied to investigate two representative GBCAs in the presence of Zn2+ and heparin, which is used as a model for a macromolecular and physiologically occurring chelator. Opposing indirect impacts of heparin on increasing the kinetic stability but reducing the thermodynamic stability of GBCAs are observed. The relaxivity of resulting Gd-heparin complexes is shown to be essentially increased compared to that of the parent GBCAs so that they might be one explanation for observed long-term MRI signal enhancement in vivo. In forthcoming studies, the presented method could help to identify the most potent Gd-complexing macromolecular species.
format	article
author	Patrick Werner Matthias Taupitz Leif Schröder Patrick Schuenke
author_facet	Patrick Werner Matthias Taupitz Leif Schröder Patrick Schuenke
author_sort	Patrick Werner
title	An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
title_short	An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
title_full	An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
title_fullStr	An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
title_full_unstemmed	An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator
title_sort	nmr relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from gbcas to a competing macromolecular chelator
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/34db663745f048b2b7583c090fc8cf5c
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An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator

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