METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

肿瘤相关单抗是一种潜在的治疗药物 细胞毒剂对恶性细胞的选择性载体。我们正在测试 这一假设在几个动物模型系统中都存在。 所使用的杀细胞剂是各种放射性核素。他们的 与单抗结合时的相对效力是 与单独或结合的单抗的检测结果进行比较 为了毒素。选择用于研究的几种放射性核素的范围包括 可用的放射性核素特性。 最近的研究集中在Y-90的临床应用上，以及 用发射核素的阿尔法粒子完成临床前研究 铋-212和铋-213。 最近，我们在#年的辐射实验室安装了一个热室 订购TB使高活性(&gt；10 mci)剂量的抗体标记 用铋-212阿尔法粒子发射器。黄曲霉毒素的毒性研究 铋-212-抗体剂量正在猴子身上进行。目前，4剂MCI剂量 几乎没有表现出血液或其他毒性。根据这些数据，一项指数 将建设用于治疗白血病患者的医院。 这样的研究正在为人类医学提供一个设计的基础 选择性靶向杀伤细胞治疗恶性肿瘤的合理治疗 治疗肿瘤以及转移的药物，并将另外允许 改进了对恶性肿瘤的诊断成像。

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. Recent research has focused on clinical use of Yttrium-90, and on completing preclinical studies with the alpha particle emitting nuclides Bismuth-212 and Bismuth-213. Most recently, we have installed a Hot Cell in the radiation laboratory in order tb make high level activity (>10 mCi) doses of antibodies labeled with the Bismuth-212 alpha particle emitter. Studies of toxicity of Bismuth-212-antibody doses is underway in monkeys. Currently, 4 mCi doses have shown almost no blood or other toxicity. Based on these data, an IND for treatment of leukemia patients will be constructed. 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.