Hubertus Pietsch PhD, Presenter: Employee, Bayer AG

Jakob Walter DVM, Abstract Co-Author: Nothing to Disclose

Thomas Frenzel PhD, Abstract Co-Author: Employee, Bayer AG, Berlin, Germany

Hans J. Weinmann PhD, Abstract Co-Author: Employee, Bayer AG

Martin Sieber PhD, Abstract Co-Author: Nothing to Disclose

Nephrogenic systemic fibrosis (NSF) is an acquired, idiopathic disorder observed only in patients with severe renal dysfunction. The cuteneous findings in NSF patients are characterized by skin thickening, infiltration of CD34+ cells and increase in collagen bundles. Recently, several publications suggested a relationship between the administration of Gd -based CA (predominantly Gadodiamide (Omniscan®)) and the occurrence of NSF. The objective of this preclinical study was to investigate the potential of various Gadolinium-chelates to release Gadolinium in vivo and to evaluate their potential to induce NSF.

Clinically used extra cellular Gd– containing contrast agents (Gd-DTPA (Magnevist®), Gadobutrol (Gadovist®), Gadodiamide (Omniscan®), Gadoversetamide (Optimark®), Gd-BOPTA (Multihance®), Gd-DOTA (Dotarem®)) were tested in a subchronic toxicity study in rats. The animals received i.v. injections at a dose of 2.5 mmol Gd/kg five times per week for four weeks. Animals were examined daily regarding pathologic findings and were sacrificed 5 days after the last injection. Histopathology of the skin was evaluated and the Gd-concentration in various tissues measured. In addition electron microscopy combined with energy dispersive spectroscopy was performed.

In rats a high exposure to the contrast agents was achieved by daily injections, similar to the situation in patients with severe renal dysfunction,. Macroscopic and microscopic findings (fibrosis and infiltration of CD34+ cells) in the skin were observed only in the animals treated with Gadodiamide (Omniscan®) and were associated with very high Gd concentration in the skin. In this lesions Gd-deposits were detected in electron microscopy.

The used animal model was an appropriate tool to investigate differences between various Gd-chelates regarding their risk to accumulate in tissue and trigger NSF-like skin lesions.

NSF like skin lesions were only observed after treatment with Gadodiamide (Omniscan®) and associated with a high Gd concentration in the skin.

Pietsch, H, Walter, J, Frenzel, T, Weinmann, H, Sieber, M, Comparison of Gd-containing MRI Contrast Agents: Their in Vivo Stability and Potential Role in the Pathogenesis of NSF.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5008573.html