METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

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。 最近的研究集中在钇-90的临床应用上， 完成α粒子放射核素的临床前研究 铋-212和铋-213。 最近，我们在辐射实验室安装了一个热室， 为了制备高水平活性（>10 mCi）剂量的标记抗体， 使用了铋-212阿尔法粒子发射器 的毒性研究 Bisphosphate-212-抗体剂量正在猴子中进行。 目前，4 mCi剂量 几乎没有血液或其他毒性。 根据这些数据， 用于治疗白血病患者。 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。

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.