Premium
The Role of Equilibrium and Kinetic Properties in the Dissociation of Gd[DTPA‐bis(methylamide)] (Omniscan) at near to Physiological Conditions
Author(s) -
Baranyai Zsolt,
Brücher Ernő,
Uggeri Fulvio,
Maiocchi Alessandro,
Tóth Imre,
Andrási Melinda,
Gáspár Attila,
Zékány László,
Aime Silvio
Publication year - 2015
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/chem.201405967
Subject(s) - chemistry , bicarbonate , dissociation (chemistry) , dissociation constant , ion , analytical chemistry (journal) , chromatography , biochemistry , receptor , organic chemistry
[Gd(DTPA‐BMA)] is the principal constituent of Omniscan, a magnetic resonance imaging (MRI) contrast agent. In body fluids, endogenous ions (Zn 2+ , Cu 2+ , and Ca 2+ ) may displace the Gd 3+ . To assess the extent of displacement at equilibrium, the stability constants of DTPA‐BMA 3− complexes of Gd 3+ , Ca 2+ , Zn 2+ , and Cu 2+ 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 m M [Gd(DTPA‐BMA)]) was found to be 17 % by the formation of Gd(PO 4 ), [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 m M ) at pH 7.4. Transmetallation reactions between [Gd(DTPA‐BMA)] and Cu 2+ 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 Gd III complex in body fluids depending on the rate of elimination of the contrast agent.