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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalJournal of Nuclear Medicine
Volume51
Issue number6
DOIs
StatePublished - 1 Jun 2010

Keywords

  • Anti-PEG reporter
  • Humanized anti-PEG reporter
  • Noninvasive imaging
  • PEGylated imaging probes
  • Polyethylene glycol

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