The Bioinorganic and Bioorganometallic Chemistry of Radionuclides and Boron Clusters

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Molecular imaging (MI) is revolutionizing diagnostic medicine, drug discovery and basic disease research by making it possible to visualize biological processes non-invasively. MI involves an imaging modality and specially designed chemical probes that bind to and reveal specific biological targets. The use of optical, nuclear and other classes of MI probes is changing how diseases are diagnosed, drugs are developed, and is radically altering how scientists study existing and emerging biochemical systems. The Valliant group focuses on research that facilitates and expedites the discovery and preparation of novel MI probes. This is achieved by studying the chemistry of medical isotopes and boron compounds including how the latter interacts with radioactive elements used in medical imaging. Recent work involved creating new molecules that can bind medical isotopes such as technetium, which is used extensively in nuclear medicine, in a way that the resulting compounds can be made to selectively target sites of disease. The next phase of the program builds on our past discoveries to address important research questions focusing on two main areas. The first looks to add to the current understanding of boron chemistry and to use the arising knowledge to develop new kinds of MI probes. The work is based on our recent unearthing of a new way to prepare carboranes in high yield at low temperatures. Carboranes can be used to generate a unique class of compounds (metallocarboranes) in water under conditions that can be used to prepare a new generation of MI probes. New ways to make this particular class of compounds has significant added value in that carboranes are also being used to develop new materials, catalysts and inorganic pharmaceuticals. The second area involves the creation of compounds that can be used to develop luminescent and radioactive compounds having identical structures (also known as isostructural MI probes). The goal is to use the arising chemistry to create probes that make it possible to link cell and tissue imaging with whole body imaging methods thereby providing connections between understanding of cellular processes and disease detection and characterization in patients. This objective will be achieved by expanding the known chemistry of technetium and rhenium and creating classes of compounds that can be used for both optical and nuclear imaging and that can be directed to bind specific proteins. The proposed program will leverage the world-class nuclear research facilities at McMaster University, which were recently upgraded in 2010 to include a new suite of radiochemistry laboratories. McMaster is also home to an NSERC Create program in molecular imaging probes (a collaborative training program with the University of Alberta) and the Centre for Probe Development and Commercialization (CPDC) which is a national Centre of Excellence focused on translating new MI probes from the laboratory into clinical trials. The field of MI relies on probe development and advances in fundamental chemistry such as those described in the application. The outcomes of the proposed research and training program will contribute to the growth of the MI field while addressing the current shortage of highly qualified personnel in a rapidly expanding sector that is an important part of the Canadian economy and healthcare system.