The Rates of the Exchange Reactions between [Gd(DTPA)]2- and the Endogenous Ions Cu2+ and Zn2+

A Kinetic Model for the Prediction of the in Vivo Stability of [Gd(DTPA)]2- , Used as a Contrast Agent in Magnetic Resonance Imaging

L. Sarka, L. Burai, E. Brücher

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100 Citations (Scopus)

Abstract

The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = diethylenetriamine-N,N,N′,N″,N″-penta-acetic acid), used as a contrast-enhancing agent in magnetic resonance imaging (MRI), is characterised by the rates of the exchange reactions that take place with the endogenous ions Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93±0.17M-1S-1 and (5.6±0.4) × 10-2M-1 S-1, respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58±0.22M-1 s-1), and under physiological conditions the release of Gd3+ predominantly occurs through the reactions of the complex with the Cu2+ and Zn2+ ions. To interpret the rate data, the rate-controlling role of a dinuclear intermediate was assumed in which a glycinate fragment of DTPA is coordinated to Cu2+ or Zn2+. In the exchange reactions between [Gd-(DTPA)]2- and Eu3+, smaller amounts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cysteine have a catalytic effect. In a model of the fate of the complex in the body fluids, the excretion and the "dissociation" of [Gd(DTPA) ]2- are regarded as parallel first-order processes, and by 10 h after the intravenous administration the ratio of the amounts of "dissociated" and excreted [Gd(DTPA)]2- is constant. From about this time, 1.71 % of the injected dose of [Gd(DTPA)]2- is "dissociated". The results of equilibrium calculations indicate that the Gd3+ released from the complex is in the form of Gd3+-citrate.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalChemistry - A European Journal
Volume6
Issue number4
Publication statusPublished - Feb 18 2000

Fingerprint

Gadolinium DTPA
Contrast Media
Amino acids
Ions
Kinetics
Body fluids
Magnetic resonance
Acetic acid
Rate constants
Ion exchange
Protons
Imaging techniques
Pentetic Acid
Citric Acid
Acetic Acid
Glycine
Cysteine
Magnetic Resonance Imaging
Amino Acids

Keywords

  • Chelates
  • Contrast agents
  • Exchange reactions
  • Gadolinium
  • Kinetics

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

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title = "The Rates of the Exchange Reactions between [Gd(DTPA)]2- and the Endogenous Ions Cu2+ and Zn2+: A Kinetic Model for the Prediction of the in Vivo Stability of [Gd(DTPA)]2- , Used as a Contrast Agent in Magnetic Resonance Imaging",
abstract = "The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = diethylenetriamine-N,N,N′,N″,N″-penta-acetic acid), used as a contrast-enhancing agent in magnetic resonance imaging (MRI), is characterised by the rates of the exchange reactions that take place with the endogenous ions Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93±0.17M-1S-1 and (5.6±0.4) × 10-2M-1 S-1, respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58±0.22M-1 s-1), and under physiological conditions the release of Gd3+ predominantly occurs through the reactions of the complex with the Cu2+ and Zn2+ ions. To interpret the rate data, the rate-controlling role of a dinuclear intermediate was assumed in which a glycinate fragment of DTPA is coordinated to Cu2+ or Zn2+. In the exchange reactions between [Gd-(DTPA)]2- and Eu3+, smaller amounts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cysteine have a catalytic effect. In a model of the fate of the complex in the body fluids, the excretion and the {"}dissociation{"} of [Gd(DTPA) ]2- are regarded as parallel first-order processes, and by 10 h after the intravenous administration the ratio of the amounts of {"}dissociated{"} and excreted [Gd(DTPA)]2- is constant. From about this time, 1.71 {\%} of the injected dose of [Gd(DTPA)]2- is {"}dissociated{"}. The results of equilibrium calculations indicate that the Gd3+ released from the complex is in the form of Gd3+-citrate.",
keywords = "Chelates, Contrast agents, Exchange reactions, Gadolinium, Kinetics",
author = "L. Sarka and L. Burai and E. Br{\"u}cher",
year = "2000",
month = "2",
day = "18",
language = "English",
volume = "6",
pages = "719--724",
journal = "Chemistry - A European Journal",
issn = "0947-6539",
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TY - JOUR

T1 - The Rates of the Exchange Reactions between [Gd(DTPA)]2- and the Endogenous Ions Cu2+ and Zn2+

T2 - A Kinetic Model for the Prediction of the in Vivo Stability of [Gd(DTPA)]2- , Used as a Contrast Agent in Magnetic Resonance Imaging

AU - Sarka, L.

AU - Burai, L.

AU - Brücher, E.

PY - 2000/2/18

Y1 - 2000/2/18

N2 - The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = diethylenetriamine-N,N,N′,N″,N″-penta-acetic acid), used as a contrast-enhancing agent in magnetic resonance imaging (MRI), is characterised by the rates of the exchange reactions that take place with the endogenous ions Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93±0.17M-1S-1 and (5.6±0.4) × 10-2M-1 S-1, respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58±0.22M-1 s-1), and under physiological conditions the release of Gd3+ predominantly occurs through the reactions of the complex with the Cu2+ and Zn2+ ions. To interpret the rate data, the rate-controlling role of a dinuclear intermediate was assumed in which a glycinate fragment of DTPA is coordinated to Cu2+ or Zn2+. In the exchange reactions between [Gd-(DTPA)]2- and Eu3+, smaller amounts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cysteine have a catalytic effect. In a model of the fate of the complex in the body fluids, the excretion and the "dissociation" of [Gd(DTPA) ]2- are regarded as parallel first-order processes, and by 10 h after the intravenous administration the ratio of the amounts of "dissociated" and excreted [Gd(DTPA)]2- is constant. From about this time, 1.71 % of the injected dose of [Gd(DTPA)]2- is "dissociated". The results of equilibrium calculations indicate that the Gd3+ released from the complex is in the form of Gd3+-citrate.

AB - The kinetic stability of the complex [Gd(DTPA)]2- (H5DTPA = diethylenetriamine-N,N,N′,N″,N″-penta-acetic acid), used as a contrast-enhancing agent in magnetic resonance imaging (MRI), is characterised by the rates of the exchange reactions that take place with the endogenous ions Cu2+ and Zn2+. The reactions predominantly occur through the direct attack of Cu2+ and Zn2+ on the complex (rate constants are 0.93±0.17M-1S-1 and (5.6±0.4) × 10-2M-1 S-1, respectively). The proton-assisted dissociation of [Gd(DTPA)]2- is relatively slow (k1 = 0.58±0.22M-1 s-1), and under physiological conditions the release of Gd3+ predominantly occurs through the reactions of the complex with the Cu2+ and Zn2+ ions. To interpret the rate data, the rate-controlling role of a dinuclear intermediate was assumed in which a glycinate fragment of DTPA is coordinated to Cu2+ or Zn2+. In the exchange reactions between [Gd-(DTPA)]2- and Eu3+, smaller amounts of Cu2+ and Zn2+ and their complexes with the amino acids glycine and cysteine have a catalytic effect. In a model of the fate of the complex in the body fluids, the excretion and the "dissociation" of [Gd(DTPA) ]2- are regarded as parallel first-order processes, and by 10 h after the intravenous administration the ratio of the amounts of "dissociated" and excreted [Gd(DTPA)]2- is constant. From about this time, 1.71 % of the injected dose of [Gd(DTPA)]2- is "dissociated". The results of equilibrium calculations indicate that the Gd3+ released from the complex is in the form of Gd3+-citrate.

KW - Chelates

KW - Contrast agents

KW - Exchange reactions

KW - Gadolinium

KW - Kinetics

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