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

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 (approximate to 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 (H2L1-3) to form ternary complexes with fluoride, [GaL1-3F] 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 [(GaLX)-X-1] (X = OH, Cl, F) by X-ray crystallography revealed thatL(1)acted as dianionic N(2)O(2)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 [D-6]DMSO and the straightforward synthesis of [(GaLF)-F-1], it was only possible to form the radioactive analogue [F-18][(GaLF)-F-1] in low radiochemical yields.