Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Nat Med. 2011 Jan;17(1):123-9. doi: 10.1038/nm.2269. Epub 2010 Dec 12.
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.
分子 - 基因成像正在从有价值的临床前工具发展为患者管理的指南。该策略涉及将成像报告基因与互补的成像剂配对在一个系统中,该系统可用于测量基因表达或蛋白质相互作用或在体内追踪基因标记的细胞。组织特异性启动子可用于描绘某些组织中的基因表达,特别是当与适当的扩增机制结合使用时。在这里,我们表明,源自介导肿瘤进展和转移表型的啮齿动物基因的进展升高基因 3(PEG-3)启动子可用于驱动成像报告基因的选择性表达,从而使用生物发光和放射性核素基于分子成像技术在人黑色素瘤和乳腺癌的小鼠模型中检测微转移疾病。由于其强大的启动子活性、肿瘤特异性和临床转化能力,PEG-3 启动子驱动的基因表达可能代表一种用于促进癌症成像和治疗的实用新系统。