Contrast Agents & Radiotracers As Activity-Based Sensors of Faulty Metabolism

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The ability to image the biochemical changes deep inside our bodies as we progress from being healthy to being sick has revolutionized our understanding of disease. The combination of innovations in chemistry and physics has enabled this revolution, advancing both the machines and injectable chemical probes required to generate these images. One way to continue to advance our imaging capabilities is through novel chemistry controlling the physical properties of these imaging systems in new ways. The current proposal will generate new chemical approaches allowing multiple biochemical targets to be tracked at one time by Magnetic Resonance Imaging. New assemblies of nanoparticles that will manipulate light to allow the biochemistry of our blood vessels to be evaluated using Optical Coherence Tomography will also be developed. Another way to advance our imaging capabilities is to rethink how we pick what we image. Selection has largely taken a reductionist approach (e.g. expression levels of one protein), falling behind paralleled fields of biochemistry. The value of a systems-based approach has been accepted in biochemistry, which looks at the net outcome of dynamic biochemical events to define the health of the cell or tissue. To this end, we will develop a new imaging agent to report on this `net outcome' for the use of Vitamin B6, an essential enabler of more than 140 biochemical reactions. Overall, the proposed work seeks to expand the functionality of imaging with new chemical approaches, and to redefine what constitutes value in an imaging biomarker. The outcomes of this proposal are positioned to impact imaging science and our molecular understanding of disease in the short-term. New chemical platforms will enable imaging chemists and biochemists globally to evaluate of sets of biochemical targets not previously possible. Disease processes are the net outcomes of concerted biochemical pathways, and the chemistry proposed would make key information about the interaction of proteins in space and time uniquely accessible. In the longer-term, these chemical platforms for imaging probe development can have impact on clinical imaging, as all of the imaging approaches targeted herein are used daily on humans. As a result, the proposed work could positively impact imaging-based diagnostics and improve the health of Canadians. Importantly, the proposed training program will also make strides to overcome barriers to the inclusion of under-represented groups in science. With a partnership between uOttawa and a local community organization supporting Inuit families in Ottawa, we will develop science outreach providing a broad range of scientific programming tied to Inuit culture for Inuit youth.