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一种靶向癌胚抗原的纳米抗体作为非小细胞肺癌有前景的分子探针。

A nanobody targeting carcinoembryonic antigen as a promising molecular probe for non-small cell lung cancer.

作者信息

Wang Hao, Meng Ai-Min, Li Sheng-Hua, Zhou Xiao-Liang

机构信息

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.

Tianjin Shengfa NabioTech Co., Ltd., Tianjin 300457, P.R. China.

出版信息

Mol Med Rep. 2017 Jul;16(1):625-630. doi: 10.3892/mmr.2017.6677. Epub 2017 Jun 1.

Abstract

Carcinoembryonic antigen (CEA) is a biomarker and therapy target for non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer. Nanobodies with high target specificity are promising candidates to function as anti‑CEA probes. In the present study, the targeting effects of an anti‑CEA nanobody obtained from phage display were investigated using technetium‑99 m (99mTc) and fluorescence labeling. In vitro binding and immunofluorescent staining assays, as well as in vivo blood clearance and biodistribution assays were performed. High specificity and affinity of the nanobody for CEA‑positive H460 cells was observed in vitro. The pharmacokinetics assay of the 99mTc‑nanobody in Wistar rats demonstrated that the nanobody had appropriate T1/2α and T1/2β, which were 20.2 and 143.5 min, respectively. The biodistribution assay using H460 xenograft‑bearing nude mice demonstrated a high ratio of signal in tumor compared with background, which confirmed that the nanobody may be useful as a molecular probe for CEA‑positive cancer, particularly in NSCLC.

摘要

癌胚抗原(CEA)是一种生物标志物,也是非小细胞肺癌(NSCLC,肺癌最常见的类型)的治疗靶点。具有高靶向特异性的纳米抗体有望成为抗CEA探针。在本研究中,使用锝-99m(99mTc)和荧光标记研究了从噬菌体展示获得的抗CEA纳米抗体的靶向作用。进行了体外结合和免疫荧光染色试验,以及体内血液清除和生物分布试验。在体外观察到纳米抗体对CEA阳性H460细胞具有高特异性和亲和力。99mTc-纳米抗体在Wistar大鼠中的药代动力学试验表明,该纳米抗体具有合适的T1/2α和T1/2β,分别为20.2和143.5分钟。使用携带H460异种移植瘤的裸鼠进行的生物分布试验表明,与背景相比,肿瘤中的信号比例很高,这证实了该纳米抗体可能作为CEA阳性癌症的分子探针有用,特别是在NSCLC中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/207d/5482067/f3d2d7078c16/MMR-16-01-0625-g00.jpg

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