New Chelators for Less-Developed and 'Heavy' Radioactive Metal Isotopes

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This project will feature the chelate design and synthesis of a range of radionuclides for which previously very little ligand chemistry has been developed, and are situated towards the lower end of the periodic table e.g. 223Ra, 212Pb, 225Ac, 213Bi and 227Th. These radio isotopes offer a range of imaging, diagnostic and therapeutic properties which have currently been underutilised by the lack of suitable chelators, and the lack of availability of the radioisotopes themselves. Many of these metals have been utilised in their simple halide, nitrate or hydroxide compound state, but there is a real dearth of stable chelate complexes known in the literature. In this project, the student will prepare a range of macrocyclic 'crown' ligands featuring a range of donor heteroatoms either within the ring system or as pendant groups, which can enable a tailoring of the 'hard-soft' nature of the radiometals. The most promising chelators will be chosen to take forward for bioconjugation to a peptide or antibody, and subjected to a range of radiolabelling, in vitro and in vivo experiments to evaluate the biological efficacy of these new, targeted radiotracers. The synthetic chemistry will be carried out at Imperial College, whilst radiolabelling biological experiments will be undertaken at King's College and via collaborators at the National Nuclear Laboratory.