title: The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions.
abstract: [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 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 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.
authors: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4032 Debrecen, Egyetem tér 1. (Hungary). zsolt.baranyai@science.unideb.hu.
authors: Zsolt
authors: Z
authors: Baranyai
authors: Ernő
authors: E
authors: Brücher
authors: Fulvio
authors: F
authors: Uggeri
authors: Alessandro
authors: A
authors: Maiocchi
authors: Imre
authors: I
authors: Tóth
authors: Melinda
authors: M
authors: Andrási
authors: Attila
authors: A
authors: Gáspár
authors: László
authors: L
authors: Zékány
authors: Silvio
authors: S
authors: Aime
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism*; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry; D019786:Gadolinium DTPA / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008744:Methylamines / Q000737:chemistry; D004369:Pentetic Acid / Q000737:chemistry
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D008744:Methylamines; D004369:Pentetic Acid; C064925:gadodiamide; D005682:Gadolinium; C027451:methylamine; D019786:Gadolinium DTPA
keywords: complex stability; gadolinium; kinetics; magnetic resonance imaging; reaction mechanisms