Gadolinium(III) complex equilibria: the implications for Gd(III) MRI contrast agents.

A computer model of blood plasma which has allowed the effect of Gd(III) contrast agents to be simulated has been developed. Initial binding of Gd(III) is to transferrin. At high concentration the metal ion binds to citrate and salicylate. At a concentrate of 10(-3) M, GdCl3 is predicted to effect a redistribution of the in vivo Zn(II), Ca(II), and Fe(II) complexes present in blood plasma. There is little effect on the Cu(II) distribution. At a concentration below 10(-5) M EDTA and DTPA have little effect on the free Gd(III) metal ion concentration. Above this concentration though, the metal ion is bound almost exclusively to the EDTA or DTPA. An attempt is made to relate the toxicity of GdCl3, [Gd(EDTA)]-, and [Gd(DTPA)]2- to the thermodynamic stability of these complexes. The effect of substitution kinetics is also discussed.