Photoactivatable bis(thiosemicarbazone) derivatives for copper-64 radiotracer synthesis

In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine, due to their favourable and complementary decay properties. As (67)Cu and (64)Cu are chemically identical, development of both existing and new bifunctional chelators for (64)Cu imaging agents can be readily adapted for the (67)Cu-radionuclide. In this study, we explored the use of photoactivatable copper chelators based on the asymmetric bis(thiosemicarbazone) scaffold, H(2)ATSM/en, for the photoradiolabelling of protein. Photoactivatable (64)CuATSM-derivatives were prepared by both direct synthesis and transmetallation from the corresponding (nat)Zn complex. Then, irradiation with UV light in the presence of a protein of interest in a pH buffered aqueous solution afforded the (64)Cu-labelled protein conjugates in decay-corrected radiochemical yield of 86.9 ± 1.0% via the transmetallation method and 35.3 ± 1.7% from the direct radiolabelling method. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic positron emission tomography (PET) imaging and targeted radionuclide therapy.