Burak W E, DePalatis L, Nines R, Hitchcock C, Hinkle G, Houchens D, Farrar W B
Department of Surgery, College of Medicine, The Ohio State University, and The Arthur G. James Cancer Hospital and Research Institute, Columbus 43210, USA.
Nucl Med Biol. 1998 Oct;25(7):633-7. doi: 10.1016/s0969-8051(98)00028-6.
Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radio-labeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with 125I-labeled NR-LU-10 Fab (12 microg/5 microCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58+/-1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13+/-0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS system (radioimmunoguided surgery).
放射免疫检测利用肿瘤特异性或肿瘤相关的放射性标记单克隆抗体或其他生物分子来诊断癌症患者的疾病范围，迄今为止在乳腺癌患者的研究中应用有限。困难在于找到一种足够敏感和特异、能够定位到乳腺肿瘤的抗体。本研究对NR-LU-10 Fab（抗体片段）在乳腺肿瘤中的肿瘤定位及生物分布进行了免疫组化和体内评估，以确定其选择性结合恶性组织的能力。NR-LU-10 Fab识别一种在上皮细胞起源肿瘤中发现的泛癌糖蛋白抗原。NR-LU-10 Fab与6/6（100%）乳腺癌细胞系以及14/16（87.5%）乳腺肿瘤发生反应，免疫染色强度各不相同。给携带ZR-75-1乳腺癌异种移植物的无胸腺小鼠注射125I标记的NR-LU-10 Fab（12微克/5微居里），并在固定时间间隔处死。这些研究表明，注射后12小时标记的Fab在肿瘤中的摄取量最高（4.58±1.59%注射剂量/克组织 [% ID/g]）；到注射放射性标记的Fab后72小时，该摄取量逐渐降至0.13±0.05% ID/g组织。对正常组织的生物定位正如对Fab片段所预期的那样；即在清除器官（肾脏）中最初较高，随后在72小时的测试期内迅速清除。NR-LU-10 Fab在乳腺肿瘤中的定位良好，对正常组织的生物定位极少，因此支持其在放射免疫闪烁显像和RIGS系统（放射免疫导向手术）中的潜在应用。
