Grant: Discovery Grants Program - Individual

Sponges absorb water because they contain thousands of small pores ? expand the pores, and they?ll absorb more water. Tissues in the body can act in a similar way. Tumours treated with chemotherapy absorb the drug, destroying the cancer cells. What if there was a method to expand tissue pores to increase absorption and in turn effectiveness? What if this method could help go through natural blockages such as the blood-brain barrier? High-intensity focused ultrasound (HIFU) just might be the key. Researchers are currently exploring methods of using HIFU to improve or induce molecular delivery. Acoustic cavitation ? a process that uses ultrasound to expand or create pores ? and its associated micro-streaming effects from confined and localized forces are believed to be the mechanisms. This delivery method still lacks the appropriate means to guide and confirm direct effects. In this program, I propose to develop the basic research to achieve guidance for HIFU-mediated molecular delivery using molecular imaging. This approach offers two distinct benefits: it will provide biologically-specific guidance to ensure delivery to identified targets, and it can offer information about the molecular pathways that are modified (thereby monitoring response). The program builds upon previous experience in HIFU imaging guidance and molecule delivery and focuses in two topics: 1) HIFU-mediated molecule delivery followed up by small animal positron emission tomography (µPET) . I will build upon results of HIFU-mediated molecule delivery for the treatment of human papillomavirus (HPV)-infected cells. I propose to validate the use of µPET to follow up response in animals to antibody delivery targeting a protein that transforms cells. A second project will validate µPET to follow up delivery after HIFU-induced blood-brain barrier opening as a tool for enhancing enzyme replacement. As a parallel outcome, we will obtain prototypes for animal molecule delivery paired with µPET guidance. 2) Biologically-specific imaging probes for HIFU-mediated molecule delivery to prostate cancer tumours . I will work with a labelled antibody developed by my group as an MRI contrast agent, which has been successfully characterized and detected on MR images of cells and tumours. We will build upon these results to explore other markers as well as evaluate the feasibility of this agent to follow up changes after molecule delivery. The proposed projects link different disciplines and will leverage established collaborations. As with my past projects, the research also features a strong training component, providing with a multidisciplinary learning environment in which students will interact with engineers, physicists, biologists and chemists. I will build upon relationships and previous experience to offer interdisciplinary projects that enhance career opportunities for participating students.