Boerman O C, Mijnheere E P, Broers J L, Vooijs G P, Ramaekers F C
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Int J Cancer. 1991 May 30;48(3):457-62. doi: 10.1002/ijc.2910480325.
The purpose of this investigation was to determine the targeting potential of the murine monoclonal antibody (MAb) RNL-1 for human small-cell lung cancer (SCLC) in a nude mouse model. RNL-1 is preferentially reactive with SCLC and lung carcinoids, and was classified as a cluster-1 MAb as defined by the International Workshop on Small-Cell Lung-Cancer Antigens. From the intercellular location of the target antigen and its reactivity with 3T3 cells transfected with nucleic acid sequences encoding for the neural cell adhesion molecule (NCAM), it was concluded that RNL-1 is directed against NCAM. RNL-1 was radiolabelled with either 125iodine or 111indium and injected into nude mice bearing NC1-H82 SCLC xenografts. The biodistribution of the radiolabels was determined up to 120 hr post injection. Maximum tumour accretion for 111In-RNL-1 was 11.8%ID/g and 6.5%ID/g for 125I-RNL-1. The accumulation of 111In-RNL-1 could be visualized clearly by gamma scintigraphy without background subtraction techniques. Autoradiographs of whole-body sections from animals injected with 125I-RNL-1 showed that activity in the SCLC xenografts was mainly peripheral, suggesting that tumour uptake is dependent on the vascularization of the tumour tissue.
本研究的目的是在裸鼠模型中确定鼠单克隆抗体(MAb)RNL-1对人小细胞肺癌(SCLC)的靶向潜力。RNL-1优先与SCLC和肺类癌发生反应,根据小细胞肺癌抗原国际研讨会的定义,它被归类为1型单克隆抗体。从靶抗原的细胞内定位及其与转染了编码神经细胞粘附分子(NCAM)核酸序列的3T3细胞的反应性来看,得出的结论是RNL-1针对的是NCAM。RNL-1用125碘或111铟进行放射性标记,然后注射到携带NC1-H82 SCLC异种移植瘤的裸鼠体内。在注射后长达120小时测定放射性标记物的生物分布。111In-RNL-1的最大肿瘤摄取量为11.8%ID/g,125I-RNL-1为6.5%ID/g。111In-RNL-1的积累可以通过γ闪烁显像清晰地观察到,无需背景扣除技术。注射125I-RNL-1的动物全身切片的放射自显影片显示,SCLC异种移植瘤中的活性主要位于周边,这表明肿瘤摄取取决于肿瘤组织的血管形成。