CARBON ENCAPSULATED RADIONUCLIDE CHELATES

碳封装放射性核素螯合物

• 批准号: 2011272
• 负责人: JOHN M ALFORD
• 金额: $ 10万
• 依托单位: TDA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2011272
• 关键词: activation analysis; carbon; chelating agents; chemical structure; chemical synthesis; drug design /synthesis /production; high performance liquid chromatography; mass spectrometry; monoclonal antibody; radionuclides; rare earth element

Because they seek out and bind only to specific cells, monoclonal antibodies represent a powerful method for selectively carrying radionuclides to cancerous cells. Current techniques for attaching radionuclides to monoclonal antibodies rely on metal ion chelates. These often lack sufficient stability, and the radionuclide may be released by in vivo chemical processes or by the compounds that encapsulate the radioisotope inside a closed sphere of carbon. These new compounds possess extraordinary stability and should be completely inert to in vivo ion exchange processes. Recent experiments demonstrate that these complexes can easily withstand the nuclear decay energy produced by radioactive lanthanide metals used in nuclear medicine without releasing the radioactive decay products. Preliminary systemic toxicity studies show that they are relatively nontoxic in vivo. Phase I will focus on the synthesis, purification, and verification of these important properties. This will be accomplished by neutron activation of a model organometallic system containing a suitable isotope followed by complete characterization of the products produced by the neutron capture and subsequent decay processes. Phase II will focus on attaching the new compound to a monoclonal antibody and on characterizing the resulting conjugated complex. PROPOSED COMMERCIAL APPLICATION: It is expected that the Phase I research will demonstrate that these new organometallic compounds possess extraordinary resistance against release of the encapsulated radionuclide and will be superior to conventional chelates for conjugating radionuclides to monoclonal antibodies. Success in Phase II will result in a new type of radiolabel that can improve the performance of radioimmunoguided pharmaceuticals.

因为它们只寻找并结合特定的细胞，单克隆 抗体代表了选择性携带的强大方法 放射性核素对癌细胞的影响。 当前的附着技术 放射性核素到单克隆抗体依赖于金属离子螯合物。 这些通常缺乏足够的稳定性，并且放射性核素可能是 由体内化学过程或由以下化合物释放 将放射性同位素封装在封闭的碳球内。 这些 新化合物具有非凡的稳定性，应该完全 对体内离子交换过程呈惰性。 最近的实验 证明这些复合物可以轻松承受核 核能中使用的放射性镧系金属产生的衰变能 药物不释放放射性衰变产物。 初步的全身毒性研究表明，它们相对 体内无毒。 第一阶段将重点关注合成、纯化、 并验证这些重要的属性。 这将是 通过模型有机金属系统的中子活化来完成 含有合适的同位素，然后进行完整的表征 中子俘获和随后衰变产生的产物 流程。 第二阶段将重点是将新化合物附着到 单克隆抗体并表征所得缀合物 复杂的。 拟议的商业应用：预计第一阶段 研究将证明这些新的有机金属化合物 对封装的释放具有非凡的抵抗力 放射性核素，并且将优于传统的螯合物 将放射性核素与单克隆抗体结合。阶段性成功 II 将产生一种新型放射性标记，可以改善 放射免疫引导药物的性能。