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: 3853176
• 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/3853176
• 关键词: alpha radiation; antileukemic agent; antitumor antibody; athymic mouse; beta radiation; chelating agents; chemical synthesis; cytolysis; disease /disorder model; drug design /synthesis /production; immunoconjugates; laboratory mouse; monoclonal antibody; mouse leukemia; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide therapy; radionuclide imaging /scanning; radiopharmacology; viral leukemia; 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: one is a tumor virus induced leukemia of mice; another is human tumor xenographs in nude athymic mice. 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 nuclidic properties available, thus Copper-67 represents a weak, short range, low energy beta emitter, Yttrium-90 is a long range, high energy beta emitter, Bismuth-212 is a short-lived, alpha emitter and Lead-212 provides both short and long range beta emissions and the subsequent alpha emission of its Bismuth-212 daughter. The syntheses of the chelating agents required for linkage of these isotopes to antibody is now complete. A new compound, (Bi-CHX-DTPA), was synthesized and shown to be useful for labeling monoclonal antibodies with Bi-212. A therapy study in leukemic mice has been accomplished. These studies will provide for human medicine a basis for design of rational therapy of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and as well will allow improved diagnostic imaging of malignancies.

肿瘤相关单克隆抗体是潜在的治疗药物 作为恶性细胞的细胞毒剂的选择性载体。 我们是 在几个动物模型系统中检验这一假设：其中一个是肿瘤 病毒诱发小鼠白血病；另一个是人类肿瘤异种移植图 裸无胸腺小鼠。 所使用的杀细胞剂是各种放射性核素。 他们的 与单克隆抗体缀合时的相对功效正在研究中 与单独的单克隆抗体进行测定和比较，或 与毒素结合。 选择用于研究跨度的几种放射性核素 可用核素性质的范围，因此 Copper-67 代表 弱、短程、低能量 β 发射体，Yttrium-90 是长程， 高能 β 发射体，Bismuth-212 是一种短命的 α 发射体 Lead-212 提供短程和长程 β 发射，并且 随后其 Bismuth-212 子体的 α 发射。 的综合 将这些同位素与抗体连接所需的螯合剂 现在已经完成了。 合成了一种新化合物 (Bi-CHX-DTPA)，并被证明是有用的 用于用 Bi-212 标记单克隆抗体。 一项治疗研究 白血病小鼠已经完成。 这些研究将为人类医学提供设计基础 通过选择性靶向杀细胞剂合理治疗恶性肿瘤 针对肿瘤以及转移的药物也将允许改善 恶性肿瘤的影像诊断。