Gallium Fluoride Complexes with Acyclic Bispicolinic Ligands as Potential New Fluorine-18 Labelled Imaging Agents

Graphical Abstract

The potential of gallium(III) complexes with acyclic pentadentate bis-dipicolinic acid containing ligands (H₂L^1–3) to form ternary complexes with fluoride, [GaL^1–3F] was investigated with a view to developing new methods for radiolabelling molecules with fluorine-18.

Abstract

The positron-emitting radionuclide, fluorine-18, is used to radiolabel molecules to develop tracers for diagnostic imaging with positron-emission tomography. There is growing interest in the potential of using strong coordinate bonds between electropositive Ga(III) and electronegative fluoride (≈ 557 kJ/mol) to provide new methods of incorporating fluorine-18 into molecules. The potential of gallium(III) complexes with acyclic pentadentate bispicolinic acid containing ligands (H₂L^1–3) to form ternary complexes with fluoride, [GaL^1–3F] was investigated with a view to developing new methods for fluorine-18 radiolabelling. A solid-phase peptide synthesis approach was used to produce a bispicolinic acid chelator with a lysine residue. Characterisation of [GaL¹X] (X = OH, Cl, F) by X-ray crystallography revealed that L¹ acted as dianionic N₂O₂ donor to the Ga(III) with the fifth site occupied by a monodentate anion (OH^–, Cl^– or F^–). Despite its high stability in aqueous mixture and [D₆]DMSO and the straightforward synthesis of [GaL¹F], it was only possible to form the radioactive analogue [¹⁸F][GaL¹F] in low radiochemical yields.