Grant: Discovery Grants Program - Individual

This proposal concerns the basic underlying coordination chemistry of metal ions for two biomedical applications: ligand design, synthesis and characterization, metal complex synthesis and characterization, and physical studies, to best match ligands with metal ions. The proposal is basic coordination chemistry, always with the applications in mind. 1. Coordination Chemistry of Metallic Isotopes in Nuclear Medicine - Our group works together with TRIUMF, the BC Cancer Agency, and Canada's major isotope supplier Nordion to grow the potential of Nuclear Medicine radiometals. Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) are two imaging modalities that inform the early detection of disease, particularly in the area of oncology. New promising radiopharmaceuticals, more specific for disease processes, are being discovered for both PET and SPECT using our now established "pa" family of ligands, plus new oxinate and hydroxamate ligand families. In order to achieve this goal new ligand design strategies, syntheses, metal-ligand combinations for application to metal-ligand-vector, radiolabelling methods and chemistry are being discovered. Much of this advancement is made possible by the synthetic conjugation to coordinating ligands of biomolecules (e.g. peptides, lipids, oligosaccharides, oligonucleotides and antibodies) with specific and high affinity for cancer biomarkers. These ligands as viable imaging agents are being realized through the discovery of new robust, reproducible, high-yielding and rapid methods for introducing the radioisotope of choice into these biomolecules to give chemically stable entities, with a particular focus on 68Ga or 111In as potential imaging or therapy agents. A wide variety of radiometals (many lanthanides) are studied in the programme. 2. Lanthanide Compounds for Bone Resorption Disorders - Many contributing factors are known to influence the pathogenesis of bone disease with the most prominent being inadequate calcium uptake. A new class of osteoporosis drugs, including oral strontium ranelate, stimulate osteoblast proliferation and inhibit osteoclast activity; however, uncertainty regarding the potential toxicity of chronic strontium accumulation in bone may limit the utility of this product. Low doses of lanthanides (Ln), particularly lanthanum La, have been shown to act similarly to strontium ranelate and we are developing new ligands to deliver these ions to bone in vivo, in collaboration with Dean K. Wasan of the University of Saskatchewan and Prof. R. Wang of UBC's Department of Materials Engineering. Both projects could possibly lead to new medicinal agents for human treatment and diagnosis thereby being of significant benefit to Canadians.