METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DX & THERAPY

肿瘤相关单克隆抗体是潜在的治疗药物 作为恶性肿瘤细胞毒性剂的选择性载体的药物 细胞 我们正在几种动物模型中检验这一假设 系统：一个是肿瘤病毒诱导的小鼠白血病;另一个是肿瘤病毒诱导的小鼠白血病。 是在无胸腺裸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。 它们与抗体结合时的相对治疗功效 并与单克隆抗体进行比较 一个人 现在使用的同位素包括高度杀肿瘤的 α发射母体放射性同位素Pb-212或Bi-212，以及 β粒子发射器Y-90 不同的合成 螯合物和放射化学分离所需的这些 正在制定目标并将其付诸临床实践。 同位素疗法的结果正在与那些 通过使用抗体缀合的毒素或药物获得， 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，并迄今已被证明是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。 对患者进行肿瘤成像的研究已经开始。 用于治疗的Y-90标记抗体的临床前检查是 进行中。

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 emitter, 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. Studies of tumor imaging in patients has begun. Pre-clinical examination of Y-90 labeled antibodies for therapy are in progress.