BIFUNCTIONAL CHELATING AGENTS FOR GALLIUM (III)

镓 (III) 双功能螯合剂

• 批准号: 3774578
• 负责人: M W BRECHBIEL
• 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/3774578
• 关键词: carbon; chelating agents; chemical binding; chemical stability; chemical synthesis; gallium; immunoconjugates; indium; monoclonal antibody; neoplasm /cancer radionuclide therapy; radiochemistry; radionuclides; radiopharmacology

The synthesis and evaluation of bifunctional chelating agents designed to sequester Ga (III) isotopes define the general scope of the project. Taking advantage of extensive chemical literature elucidating the coordination chemistry of Ga(III), two compounds were targeted as promising candidates for attaching Ga(III) isotopes to monoclonal antibodies. The first ligand incorporates three catechol binding subunits, forms a trianionic complex with trivalent ions, and is expected to possess considerable stability under physiological conditions. The second ligand is the macrocyclic polyaminocarboxylate NOTA, which is known to form an exceptionally stable neutral complex with Ga(III). A comparison of the relative efficacy of the two very different ligands should assist the evolution of optimal chelating agents for gallium. The synthesis of a C-functionalized para-SCN-Bz-NOTA was recently completed in both C-14 labeled and in high purity C-12 form suitable for clinical experiments should the need arise. With both target compounds now in hand, we can begin to asses the in vitro and in vivo stability of the Ga(III) complexes and the imunoconjugates. Preliminary experts show that both compounds are efficiently labeled with In-111, and serum stability studies are underway.

双功能螯合剂设计的合成和评估 隔离GA（III）同位素定义了项目的一般范围。 利用广泛的化学文献阐明 GA（III）的协调化学，两种化合物被靶向 将GA（III）同位素连接到单克隆的有前途的候选人 抗体。 第一个配体结合了三个儿茶酚结合 亚基，形成带有三价离子的三角离子复合物，可以预期 在生理条件下具有相当大的稳定性。 这 第二配体是大环聚氨基羧酸盐NOTA，它是 已知会形成具有GA（III）的异常稳定的中性复合物。 一个 两种截然不同的配体的相对疗效的比较 应协助凝胶剂的最佳螯合剂的演变。 最近，C官能化的Para-SCN-BZ-Nota的合成是 以标记的C-14和高纯度C-12形式完成 临床实验应需要。 两种靶化合物 现在，我们可以开始对体外和体内稳定性的评估 GA（III）配合物和毫米缀合物。 初步专家展示 两种化合物均有效地用IN-111和血清标记 稳定研究正在进行中。