SOLUTION CHEMISTRY OF METAL-IONS USED IN RADIOIMMUNOTHERAPY

放射免疫治疗中使用的金属离子的溶液化学

• 批准号: 3838067
• 负责人: C G PIPPIN
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838067
• 关键词: X ray crystallography; antitumor antibody; bismuth; chelating agents; chemical kinetics; diethylenetriaminepentaacetate; ethylenediaminetetraacetate; immunoconjugates; infrared spectrometry; lead; metal complex; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; nuclear magnetic resonance spectroscopy; radiochemistry; radionuclides; radiopharmacology; radiotracer; thermodynamics; water solution; X ray crystallography; antitumor antibody; bismuth; chelating agents; chemical kinetics; diethylenetriaminepentaacetate; ethylenediaminetetraacetate; immunoconjugates; infrared spectrometry; lead; metal complex; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; nuclear magnetic resonance spectroscopy; radiochemistry; radionuclides; radiopharmacology; radiotracer; thermodynamics; water solution

The prime objective of this project is to develop an understanding of the fundamental chemistry of metal ions utilized in radioimmunotherapy, especially lead and bismuth. To accomplish this objective, we need to learn the coordination chemistry of the metal ions, in particular, their kinetic and thermodynamic behaviors in solution. This information can then be used to develop radiolabeled antibody systems for use in therapy. Substantive progress was made on two projects. First, Lead (II) complexes of the DOTA ligand were investigated in aqueous solution to model the behavior of the 212Pb alpha-particle emitter we wish to use for radioimmunotherapy of cancer. The kinetics of formation of the complex were measured and a possible mechanism for complex formation established. This information was employed to create an efficient method for labeling antibodies with 212 Pb. Secondly, the chemistry of bismuth (III) complexes with polyaminocarboxylate ligand DTPA and EDTA was investigated by physical methods including IR, NMR and X-ray diffraction. Both the CyclohexylDTPA complex which is stable in vivo and the parent DTPA complex show one carboxyl ligand that is less tightly bound than the others as evidenced in NMR spectra. The stability constant of the cyclohexyl derivative is, however, greater than that of the parent.

该项目的主要目的是建立对 用于放射免疫疗法的金属离子的基本化学， 尤其是铅和需要氏菌。 为了实现这一目标，我们需要 特别了解金属离子的协调化学反应 溶液中的动力学和热力学行为。 此信息可以 然后用于开发用于治疗的放射性标记抗体系统。 两个项目取得了实质性进展。 首先，铅（ii） 在水溶液中研究了DOTA配体的复合物 建模我们希望使用的212pbα粒子发射极的行为 癌症的放射免疫疗法。 复合物形成的动力学 测量并建立了复杂形成的可能机制。 该信息被用来创建一种有效的标签方法 212 pb的抗体。 其次，与 通过物理研究了聚氨基辅助配体DTPA和EDTA 包括IR，NMR和X射线衍射在内的方法。 两者都有环enydtpa 体内稳定的复合物和父dtpa复合物显示一个 羧基配体比其他羧基绑定不太紧密 在NMR光谱中。 环己基衍生物的稳定性常数为 但是，大于父母。