SOLUTION CHEMISTRY OF GALLIUM AND INDIUM 3-HYDROXY-4-PYRIDINONE COMPLEXES INVITRO AND INVIVO

A series of complexes of several 3-hydroxy-2-methyl-4-pyridinones with gallium(III) and indium(III) have been characterized by Potentiometric (glass electrode) titration. The equilibria have been examined at 25.0 ± 0.1 °C and at an ionic strength of μ = 0.15 M (NaCl). The pyridinones have different substituents at the ring nitrogen atom: R = H, CH3, and C2H5. These ligands form MLn complexes (n = 1–3) of great stability; the overall stability constants β3 for the 3:1 complexes are ~1038 (M = Ga) and ~1033 (M = In). The effective formation constants (β3eff) of the various ligands for Ga3+ at physiological pH are close to 1031. As a practical application of these data, comparative metal binding in a simple blood plasma model is simulated. This result is incorporated into the design of biodistribution experiments in mice using these ligands, their n-C6H13 analogue, and l-mimosine. These studies show that the amount of ligand required to prevent removal of 67Ga from 67GaL3 complexes can be reliably calculated. The 67GaL3 complexes show rapid excretion of the radionuclide through the kidneys in a rabbit. © 1990, American Chemical Society. All rights reserved.