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Open Access 01-10-2008 | Contrast Media

Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

Authors: Martin A. Sieber, Philipp Lengsfeld, Thomas Frenzel, Sven Golfier, Heribert Schmitt-Willich, Fred Siegmund, Jakob Walter, Hanns-Joachim Weinmann, Hubertus Pietsch

Published in: European Radiology | Issue 10/2008

Abstract

Recent reports suggest that nephrogenic systemic fibrosis (NSF) is associated with the administration of gadolinium (Gd)-based contrast agents (GBCAs) and in particular with the stability of the Gd-complex. The aim of this investigation was to compare GBCAs and their potential to trigger NSF. Forty-two healthy male rats received repeated intravenous injections of six different GBCAs at high doses to simulate the exposure seen in patients with severe renal dysfunction. Histopathological and immunohistochemical analysis of the skin was performed, and the concentrations of Gd, zinc and copper were measured in several tissues by inductive coupled plasma atomic emission spectroscopy. Macroscopic and histological skin changes similar to those seen in NSF patients were only observed in rats receiving Omniscan. In addition, very high concentrations of Gd were observed in the animals treated with Omniscan, and, to a lesser extent, in animals treated with OptiMARK. Significantly lower levels of Gd were found after the treatment with ionic linear agents and even less after the treatment with macrocyclic agents. The data in this investigation strongly suggest that the stability of the Gd-complex is a key factor for the development of NSF-like symptoms in this experimental setting.

However, the actual term ‘Nephrogenic Systemic Fibrosis’ was introduced much later.

As it is easy to confuse the different agents due to the very similar generic names and chemical abbreviations, as happened in the key publication by Grobner et al. [6], we have opted for using in this publication only the brand names as only the marketed formulations are investigated.

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Title: Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions
Authors: Martin A. Sieber
Philipp Lengsfeld
Thomas Frenzel
Sven Golfier
Heribert Schmitt-Willich
Fred Siegmund
Jakob Walter
Hanns-Joachim Weinmann
Hubertus Pietsch
Publication date: 01-10-2008
Publisher: Springer-Verlag
Published in: European Radiology / Issue 10/2008
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-008-0977-y

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Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

Abstract

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Abstract

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