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

Sieber, Martin; Lengsfeld, Philipp; Frenzel, Thomas; Golfier, Sven; Schmitt‐Willich, Heribert; Siegmund, F.; Walter, Jakob; Weinmann, Hanns‐Joachim; Pietsch, Hubertus

doi:10.1007/s00330-008-0977-y

Cited by 181 publications

(158 citation statements)

References 31 publications

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“…The agents with the highest in vitro stability, the macrocyclic agents, will likely have the lowest risk for releasing Gd. In a separate study we have investigated different GBCAs, confirming this ranking (29).…”

Section: Discussionsupporting

confidence: 61%

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Sieber

Lengsfeld

Walter

et al. 2008

Magnetic Resonance Imaging

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Purpose:To investigate the role of excess ligand present in gadolinium (Gd) -based contrast agents in the development of nephrogenic systemic fibrosis (NSF). Using a dosing regimen to simulate the exposure seen in patients with severe renal impairment, we investigated the effect of excess ligand on Gd-deposition and the depletion of endogenous ions. Materials and Methods:Gadodiamide and gadoversetamide were formulated with 0%, 5%, and 10% excess ligand. Forty-two, healthy, male Hannover Wistar rats received daily intravenous injections of each formulation over a period of 20 days. At the end of the study, histopathological analysis of the skin was performed and the concentrations of Gd, Zn, and Cu were measured in several tissues. The levels of Zn in the urine were also measured. Results:The most severe skin lesions were observed after injection of formulations containing 0% free ligand and in those animals with the highest Gd concentrations in the skin. There were no significant reductions in the levels of Zn or Cu observed in the skin; however, the levels of Zn in the urine were elevated following administration of formulations with the highest amount of excess ligand. Conclusion:Our findings suggest that there is an inverse correlation between the amount of excess ligand present in Gd-containing contrast agents and the amount of Gd in the tissue, and further underline the importance of the inherent stability of these agents in the development of NSF.

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Section: Discussionsupporting

confidence: 61%

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Sieber

Lengsfeld

Walter

et al. 2008

Magnetic Resonance Imaging

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“…Rats treated with Omniscan, but not other marketed GBCAs, developed a fibrosing dermopathy that was similar in many aspects to lesions in NSF patients (13). The rats showed increased dermal cellularity composed of dendritic-like cells and spindle-shaped fibrocytes (probably fibroblasts) (11,13) similar to those observed in human NSF patients (5).…”

Section: Nsf Animal Modelsmentioning

confidence: 85%

“…In a different rat study, skin lesions seen after Omniscan and gadodiamide (Omniscan without excess ligand) treatment were attributed to excessive scratching rather than an NSF-like disease process (23). This hypothesis seems unlikely since, in several studies, the increased cellularity but also the infiltration of CD34-positive was also observed after GBCAs injection in animals without ulcerations (11)(12)(13)24). The infiltration of CD34-positive fibroblast is also one of the most obvious histopathological similarities between human NSF and rat pathology.…”

Section: Nsf Animal Modelsmentioning

confidence: 99%

“…Renal impairment leads to an increase in GBCA exposure due to a prolonged circulation time in the body (21,22). This prolonged exposure can be simulated in animal experiments, either through the use of high doses of GBCA (ie, multiple injections), or by inducing renal impairment, for example, by surgical means (13).…”

Section: Nsf Animal Modelsmentioning

confidence: 99%

“…The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on the animal experiments performed in our laboratory (11)(12)(13)(14)(15)(16)(17)(18). The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.…”

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Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

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Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

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Stability and Toxicity of Contrast Agents

Brücher

Tircsó

Baranyai

et al. 2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

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Magnetic Resonance Imaging (MRI) derives directly from the phenomenon of Nuclear Magnetic Resonance (NMR [1][2][3][4]), which is widely used by chemists to determine molecular structure. The word "nuclear" was dropped in the switch to imaging to avoid alarming patients as NMR has nothing to do with radioactivity. This book is intended mainly for chemists, who are generally familiar with the NMR spectra. After a brief overview of the technique explaining the notion of relaxation time and saturation transfer used in MRI, we will describe localization techniques, which are less well-known in chemistry. The purpose of this short chapter is not to provide a complete theory of MRI [5][6][7][8], but to understand the rest of the book concerning the action of contrast agents. We will not go into the theoretical background of the phenomena, and while it is important to have some understanding of quantum mechanics, it is not our purpose to develop this aspect. This is a "nuts and bolts" description of MRI. Whenever possible, we refer to chemists' knowledge of NMR (for example, "2D NMR"). Theoretical basis of NMR Short description of NMRIn most cases, MRI focuses on one type of atomic nucleus, that of hydrogen in H 2 O. We will therefore only use this nucleus, termed the " 1 H proton."The physical phenomenon of NMR lies at the boundary between "conventional" and "quantum" treatment due to the small transition energies involved. Traditionally, the 1 H proton can be considered as a charged

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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

Cited by 181 publications

References 31 publications

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Stability and Toxicity of Contrast Agents

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