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-) (H(5)DTPA= diethylenetr iamine -N,N,N',N ",N "-penta-acetic acid), used as a contrast-enhancing age nt in magnetic resonance imaging (MRI), is characterised by the rates of th e exchange reactions that take place with the endogenous ions Cu2+ and Zn2. The reactions predominantly occur through the direct attack of Cu2+ and Z n2+ on the complex (rate constants are 0.93 +/- 0.17M(-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 (k(1) = 0.58 +/- 0.22 M-1 s(-1)), and under physiological conditions the release of Gd3+ predominantly occurs th rough the reactions of the complex with the Cu2+ and Zn2+ ions. To interpre t 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 amoun ts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cy steine have a catalytic effect. In a model of the fate of the complex in th e body fluids, the excretion and the "dissociation" of [Gd(DTPA)](2-) are r egarded as parallel first-order processes, and by 10h 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 ind icate that the Gd3+ released from the complex is in the form of Gd3+-citrat e.