The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions

Z. Baranyai, E. Brücher, Fulvio Uggeri, Alessandro Maiocchi, Imre Tóth, Melinda Andrási, A. Gáspár, László Zékány, Silvio Aime

Research output: Contribution to journalArticle

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Abstract

[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 DTPABMA3- 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(DTPABMA)] (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.

Original languageEnglish
Pages (from-to)4789-4799
Number of pages11
JournalChemistry - A European Journal
Volume21
Issue number12
DOIs
Publication statusPublished - Mar 16 2015

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gadodiamide
Pentetic Acid
Kinetics
Body fluids
Ions
Phosphates
Bicarbonates
Citric Acid
Contrast Media
Capillary electrophoresis
Magnetic resonance
Blood
Ligands
Plasmas
Imaging techniques

Keywords

  • Complex stability
  • Gadolinium
  • Kinetics
  • Magnetic resonance imaging
  • Reaction mechanisms

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions. / Baranyai, Z.; Brücher, E.; Uggeri, Fulvio; Maiocchi, Alessandro; Tóth, Imre; Andrási, Melinda; Gáspár, A.; Zékány, László; Aime, Silvio.

In: Chemistry - A European Journal, Vol. 21, No. 12, 16.03.2015, p. 4789-4799.

Research output: Contribution to journalArticle

Baranyai, Z. ; Brücher, E. ; Uggeri, Fulvio ; Maiocchi, Alessandro ; Tóth, Imre ; Andrási, Melinda ; Gáspár, A. ; Zékány, László ; Aime, Silvio. / The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions. In: Chemistry - A European Journal. 2015 ; Vol. 21, No. 12. pp. 4789-4799.
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abstract = "[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 DTPABMA3- 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(DTPABMA)] (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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AU - Uggeri, Fulvio

AU - Maiocchi, Alessandro

AU - Tóth, Imre

AU - Andrási, Melinda

AU - Gáspár, A.

AU - Zékány, László

AU - Aime, Silvio

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