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

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): John P. Prybylski, Richard C. Semelka, Michael Jay
PurposeTo 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.MethodsData 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.ResultsThe 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.ConclusionsEstimation 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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