METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

肿瘤相关单抗是潜在的治疗药物 作为细胞毒剂对恶性肿瘤细胞的选择性载体。我们是 在几个动物模型系统中验证这一假设。 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。因此，铜-67是一种弱、短 射程贝塔发射器。Y-90是一种远程、高能量的贝塔发射器 而铋-212是一种短程阿尔法发射器。 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。功效是 例外的是，疾病的完全缓解是在没有 毒性的组织学证据。我们目前正在设计一种 扩大工艺，为未来提供更大剂量的铋-212 将涉及安装和使用热室的临床试验。 我们预计这一设施将在下一财年内投入使用 年。 这样的研究正在为人类医学提供设计的基础 通过选择性靶向杀伤细胞来合理治疗恶性肿瘤 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. Thus, Copper-67 is a weak, short range beta emitter. Yttrium-90 is a long range, high energy beta emitter and Bismuth-212 is a short range alpha emitter. 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. We are currently engineering a scaled-up process to deliver larger doses of Bismuth-212 for future clinical trials which will involve installation and use of a hot cell. We anticipate that this facility will be on-line within the next fiscal year. 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.