The Bioinorganic and Bioorganometallic Chemistry of Radionuclides and Boron Clusters

放射性核素和硼簇的生物无机和生物有机金属化学

• 批准号: RGPIN-2014-04071
• 负责人: Valliant, John
• 金额: $ 4.95万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632699
• 关键词: Bioinorganic; Bioorganometallic; Chemistry; Radionuclides; Boron

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.

分子成像通过非侵入性地可视化生物过程，正在给诊断医学、药物发现和基础疾病研究带来革命性的变化。MI涉及一种成像模式和特殊设计的化学探针，这些探针结合并揭示特定的生物目标。光学、核和其他类别的MI探针的使用正在改变疾病的诊断方式、药物的开发方式，并正在从根本上改变科学家研究现有和新兴生化系统的方式。Valliant集团专注于促进和加速发现和准备新型MI探测器的研究。这是通过研究医用同位素和硼化合物的化学，包括后者如何与医学成像中使用的放射性元素相互作用来实现的。最近的工作包括创造能够与医用同位素结合的新分子，如在核医学中广泛使用的锶，其结果化合物可以选择性地靶向疾病部位。该计划的下一阶段以我们过去的发现为基础，解决两个主要领域的重要研究问题。第一个目标是增加目前对硼化学的理解，并利用所产生的知识来开发新类型的MI探针。这项工作是基于我们最近发现的一种在低温下高产率制备碳硼烷的新方法。在可用于制备新一代MI探针的条件下，碳硼烷可用于在水中生成一类独特的化合物(金属碳硼烷)。制造这类特殊化合物的新方法具有显著的附加值，因为碳硼烷也被用于开发新材料、催化剂和无机药物。第二个领域涉及创建可用于开发具有相同结构的发光化合物和放射性化合物(也称为等结构MI探针)的化合物。其目标是利用正在产生的化学物质来创造探针，使细胞和组织成像与全身成像方法相联系，从而在理解细胞过程与患者的疾病检测和特征之间提供联系。这一目标将通过扩大已知的氚和Re的化学，并创造可用于光学和核成像并可直接与特定蛋白质结合的化合物类别来实现。拟议中的计划将利用麦克马斯特大学的世界级核研究设施，这些设施最近在2010年进行了升级，包括一套新的放射化学实验室。麦克马斯特还拥有NSERC分子成像探针创建计划(与艾伯塔大学合作的培训计划)和探针开发和商业化中心(CPDC)，这是一个专注于将实验室的新MI探针转化为临床试验的国家卓越中心。MI领域依赖于基础化学方面的探针开发和进展，如申请中描述的那些。拟议的研究和培训计划的结果将有助于MI领域的增长，同时解决作为加拿大经济和医疗体系重要组成部分的快速扩张的行业目前缺乏高素质人员的问题。