Gadolinium-containing magnetic resonance contrast media: Investigation on the possible transchelation of Gd3+ to the glycosaminoglycan heparin

  • Taupitz M
  • Stolzenburg N
  • Ebert M
 et al. 
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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 W , OptiMARK W and Magnevist W , 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 W , Dotarem W and Prohance W , 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.

Author-supplied keywords

  • Complex stability
  • Contrast media
  • Gadolinium
  • Glycosaminoglycans
  • Magnetic resonance imaging
  • Nephrogenic systemic fibrosis
  • Transchelation
  • Transmetallation

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  • Matthias Taupitz

  • Nicola Stolzenburg

  • Monika Ebert

  • Jörg Schnorr

  • Ralf Hauptmann

  • Harald Kratz

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