Kwa H B, Wesseling J, Verhoeven A H, van Zandwijk N, Hilkens J
Department of Tumour Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Br J Cancer. 1996 Feb;73(4):439-46. doi: 10.1038/bjc.1996.79.
The efficacy of three murine monoclonal antibodies (MAbs) for immunoscintigraphy of small-cell lung cancer (SCLS) xenografts was studied in a Balb/c nu/nu mouse model. These Mabs, 123C3, 123A8 and MOC191, belong to cluster 1 of anti-SCLC MAbs and bind to the neural cell adhesion molecule (NCAM) with similar affinity. After intraperitoneal injection of these MAbs, labelled with 125I, the highest uptake in tumour tissue was obtained with MAb 123C3. Seven days after the administration of this MAb 13.9% of the injected dose per gram of tumour tissue was retained in the tumour. The corresponding tumour tissue ratios ranged from 3.97 for blood to 31.03 for colon. The imaging results and the tumour uptake were less favourable for the two other MAbs, 123A8 and MOC191 (fractions of injected dose respectively 6.7% and 9.2%), although affinity, biological activity after labelling and uptake in non-tumour tissues were very similar for all three MAbs. These results may be explained by the differences in the interaction between the MAbs and the tumour cells. Mab 123C3 is internalised into tumour cells, whereas both other anti-NCAM Mabs are not. Internalisation into NCI H69 cells was demonstrated in vitro by radioimmunoassay, confocal laser scanning microscopy and electron microscopy. The internalised fraction of MAb 123C3 was 22.3% after 24h, whereas this fraction was only 7.5% for MAb 123A8. Although the internalised radiolabeled Mabs are usually degraded and dehalogenated intracellularly, the retained radioactivity is high. Apparently, intracellular degradation of radiolabelled MAb 123C3 and subsequent secretion of radioactive iodine did not prevent the accumulation of intracellular radioactivity. In conclusion, accumulation and retention of radioactivity in the tumour tissue, due to internalisation of radiolabelled MAbs, may improve the results immunoscintigraphy.
在Balb/c裸鼠模型中研究了三种鼠单克隆抗体（MAb）用于小细胞肺癌（SCLS）异种移植瘤免疫闪烁显像的疗效。这些单克隆抗体123C3、123A8和MOC191属于抗SCLC单克隆抗体的第1组，以相似的亲和力与神经细胞黏附分子（NCAM）结合。腹腔注射用125I标记的这些单克隆抗体后，单克隆抗体123C3在肿瘤组织中的摄取量最高。给予该单克隆抗体7天后，每克肿瘤组织中保留了13.9%的注射剂量。相应的肿瘤组织与其他组织的比值范围从血液的3.97到结肠的31.03。另外两种单克隆抗体123A8和MOC191的显像结果和肿瘤摄取情况较差（注射剂量的分数分别为6.7%和9.2%），尽管所有三种单克隆抗体的亲和力、标记后的生物活性以及在非肿瘤组织中的摄取情况非常相似。这些结果可能由单克隆抗体与肿瘤细胞之间相互作用的差异来解释。单克隆抗体123C3被内化到肿瘤细胞中，而另外两种抗NCAM单克隆抗体则不会。通过放射免疫测定、共聚焦激光扫描显微镜和电子显微镜在体外证实了单克隆抗体123C3被内化到NCI H69细胞中。24小时后，单克隆抗体123C3的内化分数为22.3%，而单克隆抗体123A8的内化分数仅为7.5%。尽管内化的放射性标记单克隆抗体通常在细胞内被降解和脱卤，但保留的放射性很高。显然，放射性标记的单克隆抗体123C3在细胞内的降解以及随后放射性碘的分泌并没有阻止细胞内放射性的积累。总之，由于放射性标记单克隆抗体的内化作用，放射性在肿瘤组织中的积累和保留可能会改善免疫闪烁显像的结果。
