Functionalised copper-64 complexes as precursors of potential PET imaging agents for neurodegenerative disorders

A range of unsymmetrical bis(thiosemicarbazonato)zinc(II) and copper(II) complexes functionalised with structural features of the neuroactive agents dopamine and tropinone have been synthesised. The new ligands and complexes have been characterised by using mass spectrometry, elemental analysis, NMR, infrared and electronic absorption spectroscopy techniques. Transmetallation reactions of the zinc(II) analogues with ⁶⁴Cu(OAc)₂ in aqueous solution were found to be a rapid and efficient method for preparing ⁶⁴Cu-radiolabelled complexes for potential use as in vivo tracers in positron emission tomography (PET). Oxygen-dependent cellular association assays in EMT6 murine carcinoma cells revealed that despite conjugation of the tropinone group and reduced lipophilicity, the bis(thiosemicarbazonato)copper(II) complex retains hypoxia-selectively in vitro. The results demonstrate that recognised neuroactive pharmacophores can be conjugated to the bis(thiosemicarbazonato)copper(II) core as potential precursors of ⁶⁴Cu-radiopharmaceuticals for imaging of neurodegenerative disorders.