中文摘要：

目的研究抗Peroxiredoxin I（PrxI）肺腺癌相关单链抗体体外对肺腺癌细胞的增殖抑制;观察131I标记抗体在肺腺癌裸鼠模型体内分布、靶向显像及体内抑瘤作用。方法放射性核素计数法测定单链抗体细胞内摄水平;MTT法及流式细胞仪检测单链抗体抑制肺腺癌A549细胞生长情况;免疫印迹法检测单链抗体作用于A549细胞后对细胞内PrxI表达水平的影响。放射性核素131I标记纯化抗体,进行荷瘤裸鼠体内分布、SPECT放免显像及病理切片观察抑瘤作用。结果单链抗体干预后细胞PrxI蛋白表达水平较对照组下降（P〈0.05）。体内分布研究表明单链抗体与肺腺癌组织有效结合。荷瘤裸鼠尾静脉注射131I标记抗体48h后,瘤/血和瘤/肌肉放射性比值均达到最大值4.06±0.13和5.17±0.97。SPECT示抗体注射后48hT/NT值明显高于12h、24h和72h（F均〉86,P均〈0.01）。治疗4周后,131I标记抗体治疗组肿瘤体积为（0.68±0.17）cm3,质量为（1.58±0.21）g,抑瘤率56.8%,与对照组比较有统计学差异。结论抗PrxI肺腺癌单链抗体能有效抑制肺腺癌细胞生长,131I标记单链抗体在体内能抑制肿瘤生长。

英文摘要：

Objective To observe the growth inhibition and biodistribution of fully human peroxiredoxin（Prx）I-specific single chain variable fragment（scFv）antibodies from the lung adenocarcinoma-related phage antibody library.To analyze the therapeutic effect of 131I-scFv on the transplanted tumors in nude mice.Methods The detection and quantification of internalized scFv fragments were performed with radiolabeled scFv fragments.The tetrazolium salt 3（-4,5-dimethylthizaol-2-yl）-2,5-diphenyltetrazolium bromide assay （MTT）and flow cytometry （FCM）were employed to detect the growth inhibition and apoptosis of A549 cells.The protein expression of Prx I in A549 cells was analyzed by Western blot after the antibodies treatment.The tumor-beared nude mice were injected via the tail vein with purified 131I-labeled scFv.The biodistribution analysis,radioimmunoimaging and therapeutic effect analysis were taken in vivo.Results The internalized scFv resulted an antibody-mediated cell apoptosis and down-regulation of Prx I protein expression.The radiolocalization index（RI）of tumor/serum and tumor/muscle gradually increased,reaching its peak at 48 hours postadministration.The radioactivity was aggregated in tumor locations and the tumor imaging was clearly observed by single photon emission computed tomography（SPECT）imaging.The T/NT value at 48 h was significantly higher than those at 12 h,24 h and 72 h（all F 〉86,all P 〈 0.01）.The gross tumor volume of experimental group was（0.68± 0.17）cm3,the tumor weight was （1.58±0.21）g at 4 weeks after treatment.There was a significant difference between 131I-scFv group and control group.Conclusion scFv fragments against Prx I of lung adenocarcinoma had growth inhibition ability to lung adenocarcinoma cells.The 131I-scFv showed the bonding avidity specifically and therapeutic effect in vivo,implicating its potential application in lung adenocarcinoma imaging diagnosis and immunotherapy.