The stability of gadolinium-based contrast agents in human serum: A reanalysis of literature data and association with clinical outcomes |
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| Institution: | 1. Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 4012 Marsico Hall, Chapel Hill, NC 27599-7362, United States;2. Department of Radiology, UNC School of Medicine, University of North Carolina at Chapel Hill, 2001 Old Clinic Bldg., Chapel Hill, NC 27599-7510, United States;1. Department of Radiology, School of Medicine, Gazi University Ankara, Turkey;2. Department of Neurosurgery, School of Medicine, Gazi University Ankara, Turkey;1. Computational BioMedicine Laboratory, FORTH-ICS, Heraklion, Crete, Greece;2. Department of Medical Physics, University of Crete, Heraklion, Crete, Greece;3. Department of Radiology, University of Crete, Heraklion, Greece;1. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA;2. UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA, USA;3. HeartVista Inc., Los Altos, CA, USA;4. Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA;1. Magnetic Resonance Imaging Laboratory, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea;2. Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea;1. Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH 45701, United States;2. Department of Biomedical Sciences, Ohio University, Athens, OH 45701, United States;3. Department of Mechanical Engineering, Ohio University, Athens, OH 45701, United States;4. School of Rehabilitation and Communication Sciences, Ohio University, Athens, OH 45701, United States;5. Department of Geriatric Medicine, Ohio University, Athens, OH 45701, United States |
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| Abstract: | 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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