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J Nucl Med. 2010 Jun;51(6):933-41. doi: 10.2967/jnumed.109.071977. Epub 2010 May 19.

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

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  • 1Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

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 (124)I-PEG for small-animal 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 toxicity to the host. Furthermore, the humanized anti-PEG reporter 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.

PMID:
20484433
[PubMed - indexed for MEDLINE]
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