METAL CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

肿瘤相关单克隆抗体是潜在的 作为细胞毒性剂的选择性载体的治疗剂， 恶性细胞 我们正在几种动物身上检验这一假设 模型系统：一种是肿瘤病毒诱导的小鼠白血病， 另一种是在裸无胸腺小鼠中的人肿瘤异种移植物。 使用的各种杀细胞剂是放射性同位素。 当它们缀合至 抗体正在进行测定，并与单克隆抗体进行比较。 抗体单独。 现在使用的同位素包括高度 放射放射性同位素Pb-212或Bi-212的杀肿瘤α放射性母体放射性同位素 212，以及β粒子发射器，Y-90。 的合成 不同的螯合物和放射化学分离所需的 这些目标正在被设计并简化为临床 实践 同位素疗法的结果正在与 通过使用抗体缀合的毒素或药物获得的那些， 关于肿瘤生长、消退或治愈。 这些研究将为人类医学的设计提供依据 通过选择性靶向治疗恶性肿瘤 肿瘤以及转移瘤的杀细胞剂。 已经合成了用于该项目的新螯合物， 使用，并迄今已证明有用的放射生物学研究， 用α粒子标记的抗体杀死细胞并用于成像 的肿瘤。 使用In-III进行人类肿瘤成像的患者方案 标记的单克隆抗体B72.3已经启动。

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 various cytocidal agents being employed are radioisotopes. Their relative therapeutic efficacy when conjugated to antibodies is being assayed and compared to that of monoclonal antibodies alone. The isotopes now being used include the highly tumoricidal alpha emitting parent radioisotopes Pb-212 or Bi- 212, as well as the beta particle emmiter, Y-90. The syntheses of different chelates and radiochemical separations required for these objectives are being devised and reduced to clinical practice. Results from isotopic therapy are being compared with those obtained by use of antibody conjugated toxins or drugs with respect to tumor growth, regression or cure. 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. New chelates for use in this project have been synthesized and used and have thus far proven useful for radiobiology studies of cell killing with alpha particle labeled antibody and for imaging of tumors in mice. Patient protocols for imaging of human tumors by use of In-III labeled monoclonal antibody B72.3 have been initiated.