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药物 作为恶性细胞的细胞毒性剂的选择性载体。 我们 在几个动物模型系统中测试这一假设。 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 Bislane-212是一种短程阿尔法发射器 基于这些研究，一项成功的治疗成人 T细胞白血病已完成。 目前正在进行第二阶段的审判。 化合物环己基DTPA最近被测试并用于 小鼠Rauscher白血病的放射免疫治疗。 疗效 例外的是，诱导了疾病的完全缓解， 毒性的组织学证据。 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. Thus, Copper-67 is a weak, short range beta emitter. Yttrium-90 is long range, high energy beta emitter and Bismuth-212 a short range alpha emitter. Based on these studies, a successful Phase I trial of treatment of Adult T-cell Leukemia has been completed. A phase II trial is now underway. The compound cyclohexyl DTPA was recently tested and used for radioimmunotherapy of the Rauscher leukemia in mice. Efficacy was exceptional in that complete remission of disease was induced with no histological evidence of toxicity. 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.