Improved Manufacturing Process for Advanced Imaging Agents

改进先进显像剂的制造工艺

• 批准号: 7638598
• 负责人: ROBERT D BOLSKAR
• 金额: $ 37.5万
• 依托单位: TDA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7638598
• 关键词: Antioxidants; Area; Automation; Biological; Biomedical Research; Biosensor; Carbon; Chemicals; Computers; Contrast Media; Dental; Development; Diagnostic Imaging; Discipline of Nuclear Medicine; Evaluation; Fullerenes; Gadolinium; Generations; Goals; Government; Healthcare; Image; Ions; Kilogram; Lead; Magnetic Resonance Imaging; Medical; Mercuric chloride; Metals; Methods; Molecular; Oxidation-Reduction; Persons; Phase; Process; Production; Property; Protocols documentation; Research; Research Personnel; Roentgen Rays; Sampling; Small Business Innovation Research Grant; Technology; Testing; Therapeutic; Time; Work; base; chemical property; design; improved; in vivo; manufacturing process; radiotracer; research and development; sublimation; toxic metal

DESCRIPTION (provided by applicant): Endohedral metallofullerenes are spherical fullerene carbon cages confining one or more metal atoms in their interior spaces. Several promising biomedical applications that exploit the special properties of metallofullerenes are being developed, including diagnostic and imaging agents (magnetic resonance imaging (MRI) contrast agents, X-ray contrast agents, radiotracers), therapeutic nuclear medicine, antioxidants and biosensors. In our development of Gd-containing endohedral metallofullerenes as paramagentic MRI contrast agents, we recognized the need to recover all of the metallofullerenes, not just the soluble Gd@C82 metallofullerenes which comprise only 5-10% of the sublimable Gd endohedral metallofullerenes produced by the carbon arc process. In Phase II we will use our new advances in the areas of metallofullerene production and post-production processing to both increase the yield of generated metallofullerenes and to separate and purify the large majority of Gd endohedrals that the current processes cannot access, thereby increasing the yield of useful products by over a factor of ten. Improved production apparatus will be used to manufacture greater amounts of metallofullerene raw materials. Scalable processing based on a chemical redox strategy will be implemented to separate all of the available Gd metallofullerenes differentiate them into different classes based on their physical and chemical properties. Careful analytical evaluation of the obtained Gd metallofullerene fractions will be performed. These advances will benefit the development of MRI contrast applications based on metallofullerenes by generating more raw materials while separating the mixture of produced metallofullerenes into useful, homogeneous fractions.

描述（由申请人提供）：内嵌金属富勒烯是球形富勒烯碳笼，其内部空间限制了一个或多个金属原子。利用金属富勒烯的特殊性质，一些有前途的生物医学应用正在开发中，包括诊断和成像剂（磁共振成像（MRI）造影剂、X射线造影剂、放射性示踪剂）、治疗性核医学、抗氧化剂和生物传感器。在我们开发含 Gd 内嵌金属富勒烯作为顺磁性 MRI 造影剂时，我们认识到需要回收所有金属富勒烯，而不仅仅是可溶性 Gd@C82 金属富勒烯，后者仅占由碳弧工艺。在第二阶段，我们将利用我们在金属富勒烯生产和后期加工领域的新进展，既提高生成的金属富勒烯的产量，又分离和纯化当前工艺无法获得的绝大多数 Gd 内嵌体，从而提高产量有用产品的数量增加了十倍以上。改进的生产设备将用于生产更多的金属富勒烯原材料。将实施基于化学氧化还原策略的可扩展处理，以分离所有可用的 Gd 金属富勒烯，并根据其物理和化学性质将它们分为不同的类别。对获得的 Gd 金属富勒烯级分进行仔细的分析评估。这些进步将有利于基于金属富勒烯的 MRI 对比应用的发展，通过产生更多的原材料，同时将产生的金属富勒烯的混合物分离成有用的均匀部分。