Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression

被引:74
作者
Bhang, Hyo-eun C. [1 ]
Gabrielson, Kathleen L. [2 ]
Laterra, John [3 ,4 ]
Fisher, Paul B. [5 ]
Pomper, Martin G. [1 ,6 ]
机构
[1] Johns Hopkins Med Inst, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[2] Johns Hopkins Med Inst, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA
[3] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA
[4] Kennedy Krieger Inst, Baltimore, MD USA
[5] Virginia Commonwealth Univ, Massey Canc Ctr, Inst Mol Med, Dept Human & Mol Genet,Sch Med, Richmond, VA USA
[6] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
2-STEP TRANSCRIPTIONAL AMPLIFICATION; LYMPH-NODE METASTASIS; TK GENE; PHASE-I; THERAPY; DNA; ADENOVIRUS; DELIVERY; BIODISTRIBUTION; INTEGRATION;
D O I
10.1038/nm.2269
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo. Tissue-specific promoters can be used to delineate gene expression in certain tissues, particularly when coupled with an appropriate amplification mechanism. Here we show that the progression elevated gene-3 (PEG-3) promoter, derived from a rodent gene mediating tumor progression and metastatic phenotypes, can be used to drive imaging reporters selectively to enable detection of micrometastatic disease in mouse models of human melanoma and breast cancer using bioluminescence and radionuclide-based molecular imaging techniques. Because of its strong promoter activity, tumor specificity and capacity for clinical translation, PEG-3 promoter-driven gene expression may represent a practical, new system for facilitating cancer imaging and therapy.
引用
收藏
页码:123 / U302
页数:8
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