In vivo bioluminescence tumor imaging of RGD peptide-modified adenoviral vector encoding firefly luciferase reporter gene

被引:28
作者
Niu, Gang
Xiong, Zhengming
Cheng, Zhen
Cai, Weibo
Gambhir, Sanjiv S.
Xing, Lei
Chen, Xiaoyuan
机构
[1] Stanford Univ, Sch Med, Dept Radiol, MIPS, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA
关键词
adenovirus; firefly luciferase; reporter gene; integrin alpha(v)beta(3); RGD; bioluminescence imaging;
D O I
10.1007/s11307-007-0079-2
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose: The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting. Procedures: E1- and E3-deleted Ad vectors carrying firefly luciferase reporter gene under cytomegalovirus promoter (AdLuc) was surface-modified with cyclic arginine-glycine-aspartic acid (RGD) peptides through a bifunctional poly(ethyleneglycol) linker (RGD-PEG-AdLuc) for integrin alpha(v)beta(3) specific delivery. The Coxsackie and adenovirus viral receptor (CAR) and integrin alpha(v)beta(3) expression in various tumor cell lines was determined by reverse transcriptase PCR and fluorescence-activated cell sorting. Bioluminescence imaging was performed in vitro and in vivo to evaluate RGD-modified AdLuc infectivity. Results: RGD-PEG-AdLuc abrogated the native CAR tropism and exhibited significantly enhanced transduction efficiency of integrin-positive tumors than AdLuc through intravenous administration. Conclusion: This approach provides a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
引用
收藏
页码:126 / 134
页数:9
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