The stability of gadolinium-based contrast agents in human serum: A reanalysis of literature data and association with clinical outcomes

John P. Prybylski, Richard C. Semelka, Michael Jay

Research output: Research - peer-reviewArticle

Abstract

Purpose To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Methods Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logKcond) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logKcond or other stability indices were determined. Results The release curves for Omniscan®, gadodiamide, OptiMARK®, gadoversetamide Magnevist® and Multihance® were extracted and all fit well to the kinetic model. The logKconds calculated from the rate constants were on the order of ~ 4–6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Conclusions Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients.

LanguageEnglish (US)
Pages145-151
Number of pages7
JournalMagnetic Resonance Imaging
Volume38
DOIs
StatePublished - May 1 2017

Fingerprint

Gadolinium
Contrast Media
Serum
Association reactions
Kinetics
gadodiamide
gadoversetamide
Rate constants
Plasmas
Gadolinium DTPA
Half-Life
Pharmacokinetics
Phosphates
Ligands
gadobenic acid
Fluids

Keywords

  • Contrast agents
  • Gadolinium
  • Kinetics
  • Magnetic resonance imaging
  • Stability

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

Cite this

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title = "The stability of gadolinium-based contrast agents in human serum: A reanalysis of literature data and association with clinical outcomes",
abstract = "Purpose To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Methods Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logKcond) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logKcond or other stability indices were determined. Results The release curves for Omniscan®, gadodiamide, OptiMARK®, gadoversetamide Magnevist® and Multihance® were extracted and all fit well to the kinetic model. The logKconds calculated from the rate constants were on the order of ~ 4–6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Conclusions Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients.",
keywords = "Contrast agents, Gadolinium, Kinetics, Magnetic resonance imaging, Stability",
author = "Prybylski, {John P.} and Semelka, {Richard C.} and Michael Jay",
year = "2017",
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doi = "10.1016/j.mri.2017.01.006",
volume = "38",
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AU - Semelka,Richard C.

AU - Jay,Michael

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N2 - Purpose To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Methods Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logKcond) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logKcond or other stability indices were determined. Results The release curves for Omniscan®, gadodiamide, OptiMARK®, gadoversetamide Magnevist® and Multihance® were extracted and all fit well to the kinetic model. The logKconds calculated from the rate constants were on the order of ~ 4–6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Conclusions Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients.

AB - Purpose To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Methods Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logKcond) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logKcond or other stability indices were determined. Results The release curves for Omniscan®, gadodiamide, OptiMARK®, gadoversetamide Magnevist® and Multihance® were extracted and all fit well to the kinetic model. The logKconds calculated from the rate constants were on the order of ~ 4–6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Conclusions Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients.

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