The Rates of the Exchange Reactions between [Gd(DTPA)]2- and the Endogenous Ions Cu2+ and Zn2+: A Kinetic Model for the Prediction of the in Vivo Stability of [Gd(DTPA)]2- , Used as a Contrast Agent in Magnetic Resonance Imaging

L. Sarka, L. Burai, E. Brücher

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Abstract

The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = diethylenetriamine-N,N,N′,N″,N″-penta-acetic acid), used as a contrast-enhancing agent in magnetic resonance imaging (MRI), is characterised by the rates of the exchange reactions that take place with the endogenous ions Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93±0.17M-1S-1 and (5.6±0.4) × 10-2M-1 S-1, respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58±0.22M-1 s-1), and under physiological conditions the release of Gd3+ predominantly occurs through the reactions of the complex with the Cu2+ and Zn2+ ions. To interpret the rate data, the rate-controlling role of a dinuclear intermediate was assumed in which a glycinate fragment of DTPA is coordinated to Cu2+ or Zn2+. In the exchange reactions between [Gd-(DTPA)]2- and Eu3+, smaller amounts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cysteine have a catalytic effect. In a model of the fate of the complex in the body fluids, the excretion and the "dissociation" of [Gd(DTPA) ]2- are regarded as parallel first-order processes, and by 10 h after the intravenous administration the ratio of the amounts of "dissociated" and excreted [Gd(DTPA)]2- is constant. From about this time, 1.71 % of the injected dose of [Gd(DTPA)]2- is "dissociated". The results of equilibrium calculations indicate that the Gd3+ released from the complex is in the form of Gd3+-citrate.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalChemistry - A European Journal
Volume6
Issue number4
DOIs
Publication statusPublished - Feb 18 2000

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Keywords

  • Chelates
  • Contrast agents
  • Exchange reactions
  • Gadolinium
  • Kinetics

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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