TUMOR IMAGING WITH RADIOLABELLED MONOCLONAL ANTIBODY

使用放射性标记单克隆抗体进行肿瘤成像

• 批准号: 3168803
• 负责人: WIL B NELP
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168803
• 关键词: human subject; hybridomas; image processing; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer radionuclide diagnosis; peptidases; radiotracer; tumor antigens; xenotransplantation

The goal is to develop improved diagnostic imaging agents for human melanoma based on a radio-labeled monoclonal antibody. P97 and HMW are oncofetal antigens present on human melanoma tumor cells. Studies in nude mice have shown there is active concentration of both antibodies (and Fab fragments) directed against these antigens of human melanoma. Tumor labeling is antigen specific, as documented by comparisons with radiolabeled control immunoglobulin and immune fragments. Patients have been studied with whole antibody and fragments, and uptake has been documented in metastatic lesions. About 80% of documented metastatic lesions have been imaged, and antigen-specific uptake in tumor has been documented by comparison to radiolabeled control immunoglobulin. Maximum target-to-nontarget ratios observed from human tumors, biopsied at 72 hrs after intravenous administration of antibody, were 7 to 1. Fifty-five patients with advanced malignant melanoma have been studied. In addition, antibody imaging of metastatic melanoma in lymph nodes (immunolymphoseintigraphy) has begun. Antibody fragments are injected subcutaneously. In this case diseased nodes show both specific and non-specific localization of murine immunoglobulin. We are studying the details of antibody radiolabeling methods and have determined optimum conditions for preserving the immunoreactivity of labeled antibodies in relation to iodine/antibody molar ratios and all other reaction conditions, and have designed techniques to minimize radiolysis of final product. We are beginning work with antibody directed against non-small cell carcinoma of the lung. (2)

目的是开发改进的用于人类的诊断成像剂， 基于放射性标记的单克隆抗体的黑色素瘤。 P97和HMW是存在于人黑素瘤肿瘤细胞上的癌胚抗原。 对裸鼠的研究表明， 针对人的这些抗原的抗体（和Fab片段） 黑素瘤 肿瘤标记是抗原特异性的，如通过比较所记录的 放射性标记的对照免疫球蛋白和免疫片段。 患者 已经用完整的抗体和片段进行了研究， 在转移性病变中记录。 大约80%的记录转移 已经对病变进行了成像，并且已经对肿瘤中的抗原特异性摄取进行了研究。 通过与放射性标记的对照免疫球蛋白进行比较来记录。 最大 从72小时活组织检查的人肿瘤中观察到的靶与非靶比率 静脉注射抗体后，为7比1。 五十五 对晚期恶性黑色素瘤患者进行了研究。 此外，本发明还提供了一种方法， 淋巴结转移性黑色素瘤的抗体显像 （免疫荧光扫描）已经开始。 注射抗体片段 皮下注射 在这种情况下，病变的淋巴结显示出特异性和 鼠免疫球蛋白的非特异性定位。 我们正在研究 抗体放射性标记方法的详细信息，并确定了最佳 用于保持标记抗体的免疫反应性的条件， 与碘/抗体摩尔比和所有其它反应条件的关系， 并设计了技术来最大限度地减少最终产品的辐射分解。 我们 开始研究针对非小细胞癌的抗体 肺的。 （二）