Associate Professor, University of Toronto

Generously funded in honour of Dale Lewington

Project title: “Development of a Fluorescent-Photosensitizer for Real-time Imaging and Destruction of Low Grade Gliomas”

Description of the project:

Gliomas are a classification of primary brain tumour. Diagnostic images for surgery can be challenging, and so surgeons often depend on their sight and touch, which leads to uncertainty in tumour margins, causing cancerous tissue to remain post-surgery, or the removal of healthy tissue, which could be detrimental to the patient. A solution to overcome these issues is to use fluorescence-guided surgery combined with photodynamic therapy, which uses cancer-selective dyes to enhance the real-time detection/treatment of tumours during surgery. Our project describes the development of the first fluorescent chemosensor/photodynamic therapy agent for a mutant form of isocitrate dehydrogenase 1 found in 80% of low-grade gliomas. Our proposed molecule will fluoresce in gliomas but not in healthy tissue, thereby enabling rapid identification/treatment of gliomas relative to healthy tissue in patients in the operating room. If successful, clinicians can routinely employ our compound to reduce post-surgical recurrences, improve patient survival rates, and eliminate financial burdens on Canadians.

Impact of receiving the award:

My research aims to develop a fluorescent sensor and photo-therapeutic for low-grade gliomas to improve surgical resection and treatment.  The standard of care for gliomas includes maximal safe surgical resection, during which the surgeon uses pre-operative imaging combined with intraoperative navigation to identify the cancerous tissue that should be removed. However, distinguishing tumour from normal brain, particularly at the interface, is often challenging, and brain shift during surgery compromises the utility of navigation in the later stages of the operation. Recently, fluorescence-guided surgery, a technique in which cancer-selective fluorophores are used to enhance intraoperative tumour detection, has been introduced to guide and improve surgical resection. Specifically, the fluorescent probe 5-ALA has been successfully used in high-grade gliomas. However, there are no fluorescent probes for low-grade tumours, which are often the most difficult to distinguish.

Funding from Brain Tumour Foundation of Canada will help us develop a fluorescent probe for low-grade gliomas. Specifically, the award will support chemical optimization of our current molecule, which is critical for subsequent applications in glioma cell models. Our research has immense potential to advance the treatment of brain tumours by extending patients’ lives, reducing the risk of recurrence and transformation into more aggressive high-grade gliomas, and lowering patients’ financial burdens.