Development of a universal anti-polyethylene glycol reporter gene for noninvasive imaging of PEGylated probes

Kuo Hsiang Chuang, Hsin Ell Wang, Ta Chun Cheng, Shey Cherng Tzou, Wei Lung Tseng, Wen Chun Hung, Ming Hong Tai, Tien Kuei Chang, Steve R. Roffler, Tian Lu Cheng

研究成果: 雜誌貢獻文章同行評審

26 引文 斯高帕斯(Scopus)

摘要

A reporter gene can provide important information regarding the specificity and efficacy of gene or cell therapies. Although reporter genes are increasingly used in experimental and clinical studies, a highly specific yet nonimmunogenic reporter that can track genes and cells in vivo by multiple imaging technologies still awaits development. In this study, we constructed a versatile and nonimmunogenic reporter gene to noninvasively image gene expression or cell delivery by optical imaging, MRI, and small-animal PET. Methods: We cloned and expressed a membrane-anchored anti-polyethylene glycol (PEG) reporter that consists of the Fab fragment of a mouse anti-PEG monoclonal antibody, AGP3, fused to the C-like extracellular-transmembrane-cytosolic domains of the mouse B7-1 receptor. Binding of PEGylated probes (PEG-NIR797 for optical imaging, PEG-superparamagnetic iron oxide for MRI, and 124I-PEG for smallanimal PET) were examined in vitro and in vivo. In addition, we compared the specificity, immunogenicity, and probe toxicity of the anti-PEG reporter with the gold standard reporter gene, type 1 herpes simplex virus thymidine kinase (HSV-tk). Finally, we derived a humanized anti-PEG reporter and evaluated its imaging function in vivo with subcutaneous and metastatic tumor models in mice. Results: The cells or tumors that stably expressed anti-PEG reporters selectively accumulated various PEGylated imaging probes and could be detected by optical imaging, MRI, and small-animal PET. Importantly, the anti-PEG reporter displayed an imaging specificity comparable to the HSV-tk reporter but did not provoke immune responses or cause toxicitytothe host. Furthermore,the humanizedanti-PEGreporter retained high imaging specificity in vivo. Conclusion: The highly specific and nonimmunogenic anti-PEG reporter may be paired with PEGylated probes to provide a valuable system to image gene expression or cell delivery in experimental and clinical studies. COPYRIGHT

原文英語
頁(從 - 到)933-941
頁數9
期刊Journal of Nuclear Medicine
51
發行號6
DOIs
出版狀態已發佈 - 6月 2010
對外發佈

ASJC Scopus subject areas

  • 放射學、核子醫學和影像學
  • 醫藥 (全部)

指紋

深入研究「Development of a universal anti-polyethylene glycol reporter gene for noninvasive imaging of PEGylated probes」主題。共同形成了獨特的指紋。

引用此