Chelator-free peptide and protein theranostics

Peptides and proteins are privileged scaffolds for binding receptors overexpressed on the surface of cancer cells. Their combination with radioactive metals enables their use as diagnostic agents, such as 68Ga for positron emission tomography, or as therapeutic agents, such as 213Bi for targeted alpha therapy (the combination of both approaches is termed theranostics). Traditionally, this is achieved by appending large chelators, which can increase molecular size and alter charge. We have demonstrated across a range of targeting agents, including peptides, affibodies and nanobodies, that the metal can instead form an integral part of the targeting construct. This project will design peptides and small proteins targeting cancer-cell receptors such as HER-2 and PSMA to bind metals of interest for theranostics and investigate the stability of their metal complexes as well as their interactions with biological fluids and cells.