Novel probes for investigating the tumour microenvironment and tissue targeting

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The tumour microenvironment is the cellular environment in which the tumour exists and plays an important role in cancer progression and metastasis. Probe compounds that allow us to ‘see’ into cells are useful for basic biology research as well as for the diagnosis and treatment of disease. An ideal probe must be sensitive and selective towards a biological effector as well as being capable of providing a spatially resolved response in order to monitor dynamic processes within a relevant timescale. This project aims to use chemistry and medicinal chemistry approaches for increasing the half-life of the imaging agent through covalent adduct formation or by lowering passive permeability. Our prototype reaction-based probes are designed to respond chemoselectively with analytes in the tumour microenvironment such as hydrogen peroxide, hydrogen sulphide or CYP-reductase.
We anticipate the application of these reaction-based probes for basic biology research as well clinically for visualising tumours where their longer residency may positively affect image contrast and their biased tissue distribution could benefit the patient by lowering exposure of healthy tissue to radioligand. Prospective probes will be evaluated in cell-based models through collaboration with researchers at the ICR. Proof-of-concept studies will be performed in CHO cells and afterwards in colorectal and breast cancer cell lines. Finally, we will test reaction-based probes in 3D organoid mono and co-culture derived from multiple metastatic deposits of patients with metastatic bowel and gastroesophageal cancers.