Grant: Travel Awards - Institute Community Support

One of the primary reasons for cancer-related mortality is the spread of cancer cells from the primary site of growth into distant sites of the body, called metastasis. Involved in this complicated process are the increase of enzymes called proteases that enable the destruction of the tissue surrounding the cancer; increased presence of different species of proteases has been correlated with the aggressiveness of different types of cancers. Therefore, visualization and differentiation of aggressive cancers based on the presence of these proteases would give valuable information on the tumour's trajectory and growth and enable clinicians to treat these cancers quickly before their spread, decreasing the chance of mortality and morbidity in cancer patients. However, there are very few ways to image these cancers in a non-invasive manner. This research is focused on developing a new imaging agent that would target cancers that express a key protease called matriptase. Expression of matriptase has been correlated with the aggressiveness of the cancer and therefore, identifying cancers with this enzyme would be invaluable information for clinicians. We propose that an imaging agent carrying a radioactive metal that emits a signal would enable visualization of tumours that highly express matriptase. We have currently identified a number of candidates with a computer-based model of the enzyme and have moved forward with a candidate that has shown very potent binding to matriptase, representing the first example of an agent which targets matriptase for imaging. When this imaging agent is injected into mice carrying a tumour, a small signal at the site of the tumour is seen; however, the imaging agent is largely recycled from the body of the mice before reaching the tumour site. Future research is focused on stabilizing this imaging agent by modifying its chemical structure to enable higher accumulation of the imaging agent into the tumour for better imaging quality.