Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 51, Issue 6, Pages 933-941Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.109.071977
Keywords
polyethylene glycol; anti-PEG reporter; humanized anti-PEG reporter; PEGylated imaging probes; noninvasive imaging
Funding
- National Health Research Institute, Taipei, Taiwan [NHRI-EX98-9624SI]
- Academia Sinica [AS-98-TP-B09]
- National Research Program for Genomic Medicine, National Science Council, Taiwan [NSC98-3112-B-001]
- Kaohsiung Medical University Hospital Cancer Center [DOH99-TD-C-111-002]
- National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center
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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 I-124-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.
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