Four monoclonal antibodies reactive with the rod portion of human cytokeratin No. 8 were evaluated using experimental tumour radio-immunolocalization. Nude mice carrying human HeLa cell tumours were injected with 125I-labelled F(ab')2 fragments or intact IgG antibodies. Positive immunolocalization was observed with all the specific antibodies, the intact antibodies being superior to their analogous F(ab')2 fragments. High localization efficiency was observed despite the fact that the targets are intracellular filaments. The presence of necrotic areas in the tumours may favour the high uptake in the tumours. By computerized gamma-scintigraphic evaluation of the antibody distribution in the animals, several kinetic parameters of the antibody behaviour in vivo could be determined. The biological half-lives in the tumours were determined to be greater than 600 h for some of the antibodies compared to a half-life of 40-80 h in non-tumour tissues. Optimal imaging was obtained as late as 10-14 days after administration of the antibody. Up to 10% of the injected antibody could be identified in the tumours, indicating a potential value in radio-immunolocalization and radio-immunotherapy using anticytokeratin antibodies.

译文

使用实验性肿瘤放射免疫定位评估了四种与人细胞角蛋白8号杆状部分反应的单克隆抗体。向携带人类HeLa细胞肿瘤的裸鼠注射125i标记的F(ab')2片段或完整的IgG抗体。所有特异性抗体均观察到阳性免疫定位,完整抗体优于其类似的F(ab')2片段。尽管目标是细胞内细丝,但仍观察到很高的定位效率。肿瘤中坏死区域的存在可能有利于肿瘤的高摄取。通过计算机对动物中抗体分布的伽马闪烁显像评估,可以确定体内抗体行为的几个动力学参数。与非肿瘤组织中40-80 h的半衰期相比,某些抗体在肿瘤中的生物半衰期被确定为大于600 h。在施用抗体后10-14天获得最佳成像。在肿瘤中可以鉴定多达10% 的注射抗体,这表明在使用抗细胞角蛋白抗体的放射免疫定位和放射免疫治疗中具有潜在价值。

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