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.

肿瘤相关的单克隆抗体是潜在的治疗剂 作为对恶性细胞的细胞毒性剂的选择性载体。 我们是 在几种动物模型系统中检验这一假设：一个是肿瘤 病毒诱导小鼠的白血病；另一个是人类的肿瘤Xenographs 裸露小鼠。 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 分析并将其与单独的单克隆抗体进行比较或 结合到毒素。 选择用于研究跨度的几种放射性核素 可用的核素特性范围，因此铜-67代表 弱，短范围，低能β发射极，YTTrium-90是一个远距离的 高能量beta发射极，bismuth-212是一个短暂的alpha发射极 Lead-212提供了短距离和远距离的beta排放和 随后的α发射其Bismuth-212女儿。 合成 这些同位素与抗体连接所需的螯合剂 现在完成。 合成了一种新化合物（BI-CHX-DTPA），并证明很有用 用于用BI-212标记单克隆抗体。 一项疗法研究 白血病小鼠已经完成。 这些研究将为人类医学提供设计的基础 通过选择性靶向细胞杀伤的理性治疗 肿瘤的特工，转移酶以及也将允许改善 恶性肿瘤的诊断成像。