DEVELOPMENT OF NEW DIAGNOSTIC AND THERAPEUTIC TECHNIQUES USING RADIOLABELED MONOCLONAL ANTIBODIES

抗肿瘤单克隆抗体（MoAbs）有望携带放射性核素选择性靶向组织，并提供抗原特异性诊断。铟-111或碘-131标记的moab在临床上可用于恶性黑色素瘤或结直肠癌、急性心肌梗死和血管血栓形成患者的肿瘤诊断。使用in -111标记的ZCE-025检测结直肠癌的结果是令人鼓舞的，因为它可以检测到小肿瘤、CT遗漏的肿瘤和血清CEA值正常的患者的肿瘤。在整个系列中，未观察到急性或亚急性毒性。使用人/小鼠嵌合MoAbs或F(ab')_2， Fab片段显著减少了人抗小鼠抗体（HAMA）的产生。然而，肝脏和骨髓的非特异性摄取限制了标记MoAbs在诊断和治疗中的使用。通过与DTPA的螯合，用In-111标记MoAbs的技术已经允许螯合各种放射性核素，这些放射性核素对癌症的放射免疫治疗有用。

Anti-tumor monoclonal antibodies(MoAbs) are expected to carry radionuclides selectively to target tissues and to offer antigen-specific diagnosis. Indium-111 or Iodine-131 labeled MoAbs are clinically useful for the diagnosis of tumors in patients with malignant melanoma or colorectal cancer, acute myocardial infarction and vascular thrombosis using other corresponding MoAbs. The results of colorectal cancer using In-111 labeled ZCE-025 was encouraging, since it detected small tumors, tumors missed by CT and tumors in patients with normal serum CEA values. In whole series, acute or subacute toxicity was not observed. Use of human/mouse chimeric MoAbs or F(ab')_2, Fab fragments remarkably reduced the generation of human anti-mouse antibodies (HAMA). However, nonspecific uptake in liver and bone marrows limits the use of labeled MoAbs in the diagnosis and therapy. Techniques for labeling MoAbs with In-111 through the chelation with DTPA have allowed the chelating of various radionuciides useful for the radioimmunotherapy of cancer.