Coordination Chemistry of (Radio)metal Ions

该建议涉及两个生物医学应用的基本的金属离子配位化学：配体设计，合成和表征，金属配合物的合成和表征，以及物理研究，以最好地匹配配体与金属离子。 该提案是基本的配位化学，始终考虑到应用。1.核医学中金属同位素的配位化学-我们的团队与TRIUMF，BC癌症机构和加拿大主要同位素供应商Nordion合作，以提高核医学放射性金属的潜力。正电子发射断层扫描（PET）和单光子发射断层扫描（SPECT）是两种成像模式，可为疾病的早期检测提供信息，特别是在肿瘤学领域。新的有前途的放射性药物，更具体的疾病过程，正在发现PET和SPECT使用我们现在建立的“pa”家族的配体，加上新的oxinate和异羟肟酸配体家族。为了实现这一目标，正在发现新的配体设计策略、合成、用于金属配体载体的金属配体组合、放射性标记方法和化学。这种进展的大部分是通过与生物分子（例如肽、脂质、寡糖、寡核苷酸和抗体）的配位配体的合成缀合而实现的，所述生物分子对癌症生物标志物具有特异性和高亲和力。这些配体作为可行的成像剂正在通过发现新的稳健的、可重复的、高产的和快速的方法来实现，所述方法用于将选择的放射性同位素引入这些生物分子中以得到化学稳定的实体，特别关注68 Ga或111 In作为潜在的成像剂或治疗剂。 该方案研究了各种放射性金属（许多镧系元素）。 *2。用于骨吸收障碍的镧系化合物-已知有许多因素影响骨病的发病机制，其中最突出的是钙摄取不足。一类新的骨质疏松症药物，包括口服雷奈酸锶，刺激成骨细胞增殖并抑制破骨细胞活性;然而，关于骨中慢性锶蓄积的潜在毒性的不确定性可能限制该产品的实用性。低剂量的镧系元素（Ln），特别是镧La，已被证明具有与雷奈酸锶类似的作用，我们正在与Dean K.萨斯喀彻温大学的Wasan教授和R. UBC材料工程系的Wang。这两个项目都可能导致人类治疗和诊断的新药剂，从而使加拿大人受益匪浅。

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.