Cell-SELEX Aptamer for Highly Specific Radionuclide Molecular Imaging of Glioblastoma In Vivo

Xidong Wu,Xiaowen Li,Shuji Li,Yusheng Shi,Yan Tan,Chao Yuan,Xingmei Zhang,Huiyu Liang,Guiping Li,Waldemar Debinski

doi:10.1371/journal.pone.0090752

Xidong Wu, Xiaowen Li + Show 8 more

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https://doi.org/10.1371/journal.pone.0090752

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Journal: PloS one	Publication Date: Mar 6, 2014
Citations: 80	License type: CC BY 4.0

Affiliation: Southern Medical University, Nanfang Hospital

Abstract

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.

Highlights

Glioblastoma (GBM) is the most common and malignant tumor of the central nervous system with a poor overall survival of 12–14 months upon diagnosis [1,2]
The most common mutant of epidermal growth factor receptor (EGFR), EGFRvIII, which results from a deletion of the extracellular amino acids 6 to 273, occurs at an overall frequency of 25–64% when assessed by multiple techniques in GBM [4] and contributes to constitutively active oncogenic signaling that correlates with worse prognosis [5]
Selected aptamers bind to U87-EGFRvIII cells with high affinity We wondered whether the four selected aptamers (U2, U8, U19 and U31) can efficiently target U87-EGFRvIII cells

Summary

Introduction

Glioblastoma (GBM) is the most common and malignant tumor of the central nervous system with a poor overall survival of 12–14 months upon diagnosis [1,2]. Genetic alterations such as epidermal growth factor receptor (EGFR) gene amplification and mutation are main drivers promoting GBM progression and malignancy [3]. Molecular imaging, using specific molecular probes to visualize, characterize and measure biological processes at the molecular and cellular levels in humans and other living systems [9], plays a more and more important role in early diagnosis of various diseases, especially cancer, over the last decade. A variety of aptamers which are against different caner cells have been isolated from whole cell-SELEX, only a few of them have been tested for in vivo imaging [12,13]

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