Endo K, Kamma H, Ogata T
Department of Surgery, University of Tsukuba, Ibaraki-ken, Japan.
Cancer Res. 1987 Oct 15;47(20):5427-32.
A monoclonal antibody (MAb) 8 [immunoglobulin G3 (IgG3)], directed against a Mr 48,000 human lung cancer-associated antigen, was radiolabeled with either 125I or 131I, and its biodistribution was studied in nude mice bearing human lung cancer (TKB-2) over a 7-day period. 125I-labeled MAb 8 increased its binding to the tumor during the period, while the binding of 125I-labeled control IgG3 declined after initial uptake. At Day 7, percentages of injected dose of 125I-labeled MAb 8 bound to the tumor rose to 7.4%, which was a 4.4-fold increase from Day 1 and 16-fold binding of 125I-labeled control IgG3 at the same day. Tumor:blood ratios became 2.7:1 at Day 7, and tumor:liver, tumor:spleen, and tumor:kidney ratios were more than 9:1. Normal organs showed no significant uptake of 125I-labeled MAb 8, compared with those of 125I-labeled control IgG3. A clear image of the xenografted tumor was obtained at Day 5, and it further improved at Day 7, when 60% of whole body radioactivity was localized to the tumor. Autoradiography of the mouse with tumor confirmed the excellent localization of 125I-labeled MAb 8 to the tumor, although the radioactivity of the tumor was not uniformly distributed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most of the radioactivity was present at the tumor in the form of degraded immunoglobulin. MAb 8 has a potential usefulness in the diagnosis and treatment of lung cancer.
一种针对分子量为48,000的人肺癌相关抗原的单克隆抗体(MAb)8[免疫球蛋白G3(IgG3)],用125I或131I进行放射性标记,并在7天的时间内研究其在荷人肺癌(TKB - 2)裸鼠体内的生物分布。在这段时间内,125I标记的MAb 8与肿瘤的结合增加,而125I标记的对照IgG3在最初摄取后结合下降。在第7天,125I标记的MAb 8与肿瘤结合的注射剂量百分比升至7.4%,这是第1天的4.4倍,且是同一天125I标记的对照IgG3结合量的16倍。第7天肿瘤与血液的比率为2.7:1,肿瘤与肝脏、肿瘤与脾脏以及肿瘤与肾脏的比率均超过9:1。与125I标记的对照IgG3相比,正常器官对125I标记的MAb 8没有明显摄取。在第5天获得了移植瘤的清晰图像,在第7天进一步改善,此时全身放射性的60%定位在肿瘤处。对荷瘤小鼠的放射自显影证实了125I标记的MAb 8在肿瘤处的良好定位,尽管肿瘤的放射性分布不均匀。十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳分析表明,大部分放射性以降解的免疫球蛋白形式存在于肿瘤处。MAb 8在肺癌的诊断和治疗中具有潜在的应用价值。