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Gadolinium-containing magnetic resonance contrast media: investigation on the possible transchelation of Gd(3+) to the glycosaminoglycan heparin.
MedLine Citation:
PMID:  23281283     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Retention of gadolinium (Gd) in biological tissues is considered an important cofactor in the development of nephrogenic systemic fibrosis (NSF). Research on this issue has so far focused on the stability of Gd-based contrast media (GdCM) and a possible release of Gd(3+) from the complex. No studies have investigated competing chelators that may occur in vivo. We performed proton T(1) -relaxometry in solutions of nine approved GdCM and the macromolecular chelator heparin (250 000 IU per 10 ml) without and with addition of ZnCl(2) . For the three linear, nonspecific GdCM complexes, Omniscan®, OptiMARK® and Magnevist®, 2 h of incubation in heparin at 37 °C in the presence of 2.0 mm ZnCl(2) led to an increase in T(1) -relaxivity by a factor of 7.7, 5.6 and 5.1, respectively. For the three macrocyclic complexes, Gadovist®, Dotarem® and Prohance®, only a minor increase in T(1) -relaxivity by a factor of 1.5, 1.6 and 1.7 was found, respectively. Without addition of ZnCl(2) , no difference between the two GdCM groups was observed (factors of 1.4, 1.2, 1.1, 1.3, 1.5 and 1.4, respectively). The increase in T(1) -relaxivities observed for linear GdCM complexes may be attributable to partial transchelation with formation of a macromolecular Gd-heparin complex. For comparison, mixing of GdCl(3) and heparin results in a 8.7-fold higher T(1) -relaxivity compared with a solution of GdCl(3) in water. Heparin is a glycosaminoglycan (GAG) and as such occurs in the human body as a component of the extracellular matrix. GAGs generally are known to be strong chelators. Gd(3+) released from chelates of GdCM might be complexed by GAGs in vivo, which would explain their retention in biological tissues. Plasma GAG levels are elevated in end-stage renal disease; hence, our results might contribute to the elucidation of NSF. Copyright © 2012 John Wiley & Sons, Ltd.
Authors:
Matthias Taupitz; Nicola Stolzenburg; Monika Ebert; Jörg Schnorr; Ralf Hauptmann; Harald Kratz; Bernd Hamm; Susanne Wagner
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Contrast media & molecular imaging     Volume:  8     ISSN:  1555-4317     ISO Abbreviation:  Contrast Media Mol Imaging     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101286760     Medline TA:  Contrast Media Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  108-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation:
Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Benjamin Franklin, Charitéplatz 1, 10117, Berlin, Germany.
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