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.
The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = 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 Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93+/-0.17 M(-1) s(-1) and (5.6+/-0.4) x 10(-2)M(-1) S(-1), respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58+/-0.22 M(-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.
Sarka
L
L
Department of Inorganic and Analytical Chemistry, lajos Kossuth University, Debrecen, Hungary. ebrucher@tigris.klte.hu
Burai
L
L
Brücher
E
E
D003287:Contrast Media / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004355:Drug Stability; D019786:Gadolinium DTPA / Q000737:chemistry*; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008954:Models, Biological; D008962:Models, Theoretical; D015032:Zinc / Q000737:chemistry*
D003287:Contrast Media; D003300:Copper; D015032:Zinc; D019786:Gadolinium DTPA