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: 3168802
• 负责人: WIL B NELP
• 金额: $ 3.34万
• 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 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168802
• 关键词: human subject; hybridomas; image processing; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer radionuclide diagnosis; peptidases; radionuclide imaging /scanning; 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)

其目标是开发用于人类的改进的诊断显像剂 基于放射性标记的单抗的黑色素瘤。 P97和HMW是存在于人黑色素瘤细胞上的癌胎儿抗原。 在裸鼠身上的研究表明，两者都有活性浓度 针对人类这些抗原的抗体(和Fab片段) 黑色素瘤。通过比较证明，肿瘤标记是抗原特异性的。 用放射性标记的对照免疫球蛋白和免疫片段。病人 已经用完整的抗体和片段进行了研究，并且摄取了 记录在转移性病变中。约80%的有记录的转移瘤 病变已经成像，肿瘤中的抗原特异性摄取已经被 通过与放射性标记的对照免疫球蛋白进行比较而记录。极大值 从人类肿瘤中观察到的靶与非靶的比率，72小时活组织检查 静脉注射抗体后，为7至1.55 对晚期恶性黑色素瘤患者进行了研究。此外, 淋巴结转移性黑色素瘤的抗体显像 (免疫淋巴扫描)已经开始。注射抗体片段 皮下注射。在本例中，病变结节同时显示特定和 小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情况并确定了最佳方案 保存标记抗体免疫反应性的条件 与碘/抗体摩尔比和所有其他反应条件的关系， 并设计了将最终产品的辐解降至最低的技术。我们 正在开始研究针对非小细胞癌的抗体 肺脏的。(2)