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.

肿瘤相关单克隆抗体是潜在的治疗剂， 恶性细胞的细胞毒性剂的选择性载体。 我们正在测试 这一假设在几个动物模型系统。 使用的杀细胞剂是各种放射性核素。 他们的 当与单克隆抗体偶联时的相对功效被 测定并与单独的或缀合的单克隆抗体进行比较 毒素。 选择用于研究的几种放射性核素的范围为 可用的放射性核素特性。 因此，铜-67是一个弱，短， 射程β发射器 钇-90是一种长距离高能β发射体 而BISH 12 -212和BISH 13 -213是短程α粒子发射器。 最近，我们已经获得了一个放射性核素发生器的铋-213。 我们已经证明，这种来源可以成功地用于标记 已经通过连接到所述抗体上进行化学修饰的抗体， 环己基-DTPA配体。 测量了良好的标记效率。 像这样的研究为人类医学提供了设计 通过选择性靶向杀细胞剂的恶性肿瘤的合理治疗 药物治疗肿瘤，以及转移，并将另外允许 改善恶性肿瘤的诊断成像。