Comparative Transmetallation Kinetics and Thermodynamic Stability of Gadolinium-DTPA Bis-Glucosamide and Other Magnetic Resonance Imaging Contrast Media

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Abstract
The relative stability and selectivity of magnetic resonance (MR) imaging contrast agents were compared with in vitro transmetallation and ligand competition reactions. A gadolinium (Gd)-DTPA-BIGA, Gd-DTPA-BMA, Gd-DTPA, or Gd-HP-DO3A solution was mixed with an equimolar solution of zinc (Zn) citrate in 1:1 volume ratio at pH 7.4 in a transmetallation assay. In a ligand competition reaction, a DTPA or EDTA solution was mixed with an equimolar solution of Gd-DTPA-BIGA, Gd-DTPA-BMA, or Gd-HP-DO3A. The progress of the reactions was followed with high-performance liquid chromatography (HPLC) using fluorescence detection. In the transmetallation study with Zn citrate, the order of kinetic stability is Gd-HP-DO3A > Gd-DTPA > Gd-DTPA-BIGA > Gd-DTPA-BMA. The order of stability in the ligand competition reaction is Gd-HP-DO3A > Gd-DTPA-BIGA > Gd-DTPA-BMA. Transmetallation kinetics shows major differences among currently used MR imaging contrast media. Equilibrium thermodynamic constants and selectivity constants calculated therefrom do not explain the relative kinetic stability and metal selectivity of MR contrast media in the presence of competing metal ions and ligands.