Project 467227

Drug resistance is a major medical challenge leading to low survival rates amongst diseases like lung cancer, the most diagnosed cancer in Canadians. Cisplatin is the current standard of care, but drug resistance is common after 4-6 months. Recent research has found a strong association between treatment outcomes of lung tumors and the metabolism of Vitamin B6. The active form of Vitamin B6 is associated with effective chemotherapy, while the inactive form is associated with resistance. The Shuhendler group at uOttawa has previously used Vitamin B6 for detecting lung cancer resistance through contrast agents by MRI, but clinical relevance is limited due to its perturbance of natural metabolic processes. My work as a Masters candidate in Chemistry at uOttawa with Dr. Shuhendler will explore a non-invasive way to detect the onset of cancer resistance from Cisplatin-based chemotherapy using Positron Emission Tomography (PET). PET scans utilize harm-free radiotracers that collect in high metabolic activity areas like lung cancer cells, lighting up in PET scans. The project will begin by producing a modified radiotracer based on the structure of Vitamin B6. This will begin with synthetic transformation of natural Vitamin B6 metabolites at uOttawa, followed by radiolabelling at the University of Ottawa Heart Institute (UOHI) Cyclotron Facility. The next focus will be differentiating chemotherapy responsive and resistant lung cancer by PET imaging. We hope to demonstrate that reduced Vitamin B6 radiotracer retention in both cancer cells and animal model tumor tissue is associated with drug resistance. PET imaging is performed routinely in clinic, and the rapid translation of radiotracers to clinical use (18 months) suits the need for rapid response to this clinical challenge.