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The Rates of the Exchange Reactions between [Gd(DTPA)] 2− and the Endogenous Ions Cu 2+ and Zn 2+ : A Kinetic Model for the Prediction of the In Vivo Stability of [Gd(DTPA)] 2− , Used as a Contrast Agent in Magnetic Resonance Imaging
Author(s) -
Sarka L.,
Burai L.,
Brücher E.
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/(sici)1521-3765(20000218)6:4<719::aid-chem719>3.0.co;2-2
Subject(s) - chemistry , diethylenetriamine , dissociation (chemistry) , reaction rate constant , in vivo , gadolinium , ion , kinetic energy , chelation , glycine , kinetics , medicinal chemistry , inorganic chemistry , amino acid , biochemistry , organic chemistry , physics , microbiology and biotechnology , quantum mechanics , biology
The kinetic stability of the complex [Gd(DTPA)] 2− (H 5 DTPA=diethylenetriamine‐ N , N , N ′, N ″, N ″‐pentaacetic 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 Cu 2+ and Zn 2+ . The reactions predominantly occur through the direct attack of Cu 2+ and Zn 2+ on the complex (rate constants are 0.93±0.17 M −1 s −1 and (5.6±0.4)×10 −2 M −1 s −1 , respectively). The proton‐assisted dissociation of [Gd(DTPA)] 2− is relatively slow ( k 1 =0.58±0.22 M −1 s −1 ), and under physiological conditions the release of Gd 3+ predominantly occurs through the reactions of the complex with the Cu 2+ and Zn 2+ 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 Cu 2+ or Zn 2+ . In the exchange reactions between [Gd(DTPA)] 2− and Eu 3+ , smaller amounts of Cu 2+ and Zn 2+ 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 Gd 3+ released from the complex is in the form of Gd 3+ ‐citrate.