Cell-SELEX aptamer for highly specific radionuclide molecular imaging of glioblastoma in vivo.

Cell-SELEX aptamer for highly specific radionuclide molecular imaging of glioblastoma in vivo.
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用于体内胶质母细胞瘤高特异性放射性核素分子成像的 Cell-SELEX 适体

DOI:
10.1371/journal.pone.0090752
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wu X;Liang H;Tan Y;Yuan C;Li S;Li X;Li G;Shi Y;Zhang X

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胶质母细胞瘤(GBM)是最常见、最具侵袭性的成人原发性脑肿瘤,预后差.表皮生长因子受体变体III(EGFRvIII)是GBM中最常见和高度致癌的EGFR突变体。为了产生能够以高亲和力靶向EGFRvIII的特异性分子探针,我们选择了四种DNA适体(U2,U8,U19和U31),其特异性结合到U87-EGFRvIII细胞,所述U87-EGFRvIII细胞通过基于细胞的配体系统进化指数富集(cell-SELEX)过程过表达EGFRvIII,Kd值在纳摩尔范围内。引入U87 MG细胞作为对照细胞用于反向选择。进一步证实U2和U8特异性地识别靶细胞表面的EGFRvIII。然后,我们用188 Re放射性标记U2作为分子成像探针,并观察到188 Re标记的U2在小鼠中显著靶向过表达EGFRvIII的胶质母细胞瘤外移植物。结论:全细胞-SELEX策略获得的核酸适体具有作为GBM诊断的分子影像探针的潜力。
Glioblastoma (GBM) is the most frequent and aggressive primary adult brain tumor with poor prognosis. Epidermal growth factor receptor variant III (EGFRvIII) is the most common and highly oncogenic EGFR mutant in GBM. With the aim to generate specific molecular probes able to target EGFRvIII with high affinity, we selected four DNA aptamers (U2, U8, U19 and U31) specifically bound to U87-EGFRvIII cells that over expressed EGFRvIII with K d values in the nanomole range by a cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) process. U87MG cells were introduced as control cells for counter selection. We further affirmed U2 and U8 identified EGFRvIII on the surface of target cells specifically. Then we radiolabeled U2 with 188Re to serve as a molecular imaging probe and observed 188Re -labeled U2 significantly targeted EGFRvIII over-expressing glioblastoma exnografts in mice. In conclusion, aptamers obtained from whole cell-SELEX strategy have great potential as molecular imaging probes that are probably beneficial to GBM diagnoses.
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发表时间: 2013
期刊: PloS one
影响因子: 3.7
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