The Role of Equilibrium and Kinetic Properties in the Dissociation of Gd[DTPA‐bis(methylamide)] (Omniscan) at near to Physiological Conditions
2015
[Gd(DTPA-BMA)] is the principal constituent of Omniscan, a magnetic resonance imaging (MRI) contrast agent. In body fluids, endogenous ions (Zn2+, Cu2+, and Ca2+) may displace the Gd3+. To assess the extent of displacement at equilibrium, the stability constants of DTPA-BMA3− complexes of Gd3+, Ca2+, Zn2+, and Cu2+ have been determined at 37 °C in 0.15 M NaCl. The order of these stability constants is as follows: GdL≈CuL>ZnL≫CaL. Applying a simplified blood plasma model, the extent of dissociation of Omniscan (0.35 mM [Gd(DTPA-BMA)]) was found to be 17 % by the formation of Gd(PO4), [Zn(DTPA-BMA)]− (2.4 %), [Cu(DTPA-BMA)]− (0.2 %), and [Ca(DTPA-BMA)]− (17.7 %). By capillary electrophoresis, the formation of [Ca(DTPA-BMA)]− has been detected in human serum spiked with [Gd(DTPA-BMA)] (2.0 mM) at pH 7.4. Transmetallation reactions between [Gd(DTPA-BMA)] and Cu2+ at 37 °C in the presence of citrate, phosphate, and bicarbonate ions occur by dissociation of the complex assisted by the endogenous ligands. At physiological concentrations of citrate, phosphate, and bicarbonate ions, the half-life of dissociation of [Gd(DTPA-BMA)] was calculated to be 9.3 h at pH 7.4. Considering the rates of distribution and dissociation of [Gd(DTPA-BMA)] in the extracellular space of the body, an open two-compartment model has been developed, which allows prediction of the extent of dissociation of the GdIII complex in body fluids depending on the rate of elimination of the contrast agent.
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