Research Areas
Functionalised MMP Inhibitors as Radiodiagnostic, Radiotherapeutic, and Radiation-Sensitising Agents for Metastatic Cancer
Researchers: Lina Di Marco, John Doan, Brad Green
Collaborations: Assoc. Prof. Michael Kassiou of Brain and Mind Research Institute and School of Chemistry.
This project aims to develop new agents that will selectively target solid tumours based on their differing chemistry and biochemistry to healthy tissues. An important difference that has emerged recently is the overexpression of matrix metalloproteinases (MMPs) in metastasising tumours. The overexpression of MMPs on tumour cell surfaces and the fact that they occur in very low levels in healthy tissues presents a novel strategy in identifying those cells which need to be destroyed.
Most approaches to targeting radionuclides to tumour tissue have relied on radiolabelled antibodies and peptides and while there have been some promising results, the design of these types of agents remains a challenge as non-target organs such as kidney and bone marrow are still subject to high radiation doses. Targeting based on differences such as MMP overexpression has the potential to overcome many of these problems.
Schematic representation showing the principle of the delivery of a radionuclide to a tumour by means of targeting MMPs.
New analogues of MMP inhibitors are being synthesised and radiolabelled. The ability of these new agents to bind and inhibit MMPs in vitro will be tested. The aim of this project is to use the modified MMP binding agents and determine their ability to radiodiagnositically identify tumours and tumour metastases, determine the levels of MMP expression in tumours, selectively sensitise tumours to X-ray radiation, and treat tumours using attached radionuclides.