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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
Publication statusPublished - Jun 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Fingerprint Dive into the research topics of 'Development of a universal anti-polyethylene glycol reporter gene for noninvasive imaging of PEGylated probes'. Together they form a unique fingerprint.

  • Cite this

    Chuang, K. H., Wang, H. E., Cheng, T. C., Tzou, S. C., Tseng, W. L., Hung, W. C., Tai, M. H., Chang, T. K., Roffler, S. R., & Cheng, T. L. (2010). Development of a universal anti-polyethylene glycol reporter gene for noninvasive imaging of PEGylated probes. Journal of Nuclear Medicine, 51(6), 933-941. https://doi.org/10.2967/jnumed.109.071977