METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

用于肿瘤诊断和治疗的金属螯合单克隆抗体

• 批准号: 3752330
• 负责人: O A GANSOW
• 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/3752330
• 关键词: antitumor antibody; bismuth; chelating agents; copper; cytotoxicity; diethylenetriaminepentaacetate; immunoconjugates; metastasis; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide therapy; neoplastic cell; radionuclide diagnosis; radionuclide imaging /scanning; radionuclides; radiopharmacology; yttrium

Tumor associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in several animal model systems. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is being assayed and compared to that of monoclonal antibodies alone or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available. Thus, Copper-67 is a weak, short range beta emitter. Yttrium-90 is a long range, high energy beta emitter and Bismuth-212 and Bismuth-213 are short range alpha particle emitters. Most recently, we have obtained a radionuclidic generator for Bismuth-213. We have shown that this source can be successfully used for labeling antibodies that have been chemically modified by linkage to the cyclohexyl-DTPA ligand. Good labeling efficiencies were measured. Studies like these are providing for human medicine a basis for design of rational therapies of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and will in addition allow improved diagnostic imaging of malignancies.

肿瘤相关的单克隆抗体是潜在的治疗剂 细胞毒性剂对恶性细胞的选择性载体。 我们正在测试 该假设在几个动物模型系统中。 所使用的胞位剂是各种放射性核素。 他们的 与单克隆抗体共轭时相对功效 分析并与单独的单克隆抗体进行比较或共轭 到毒素。 为研究选择的几种放射性核素跨越 可提供放射性核素特性。 因此，铜-67是弱的，短的 范围Beta发射器。 YTTrium-90是远距离，高能Beta发射器 bismuth-212和二氧化碳-213是短距离α粒子发射器。 最近，我们获得了用于Bismuth-213的放射性核素发生器。 我们已经表明，该来源可以成功用于标记 通过与 环己基-DTPA配体。 测量了良好的标记效率。 这样的研究为人类医学提供了设计的基础 通过选择性靶向细胞固定的恶性肿瘤的理性疗法 肿瘤的代理以及转移酶，此外将允许 改善恶性肿瘤的诊断成像。