A novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep-tissue imaging Journal Article
| Authors: | Chen, N.; Zhang, Q.; Yu, Y. A.; Stritzker, J.; Brader, P.; Schirbel, A.; Samnick, S.; Serganova, I.; Blasberg, R.; Fong, Y.; Szalay, A. A. |
| Article Title: | A novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep-tissue imaging |
| Abstract: | Noninvasive and repetitive monitoring of a virus in target tissues and/or specific organs of the body is highly desirable for the development of safe and efficient cancer virotherapeutics. We have previously shown that the oncolytic vaccinia virus GLV-1h68 can target and eradicate human tumors in mice and that its therapeutic effects can be monitored by using optical imaging. Here, we report on the development of a derivative of GLV-1h68, a novel recombinant vaccinia virus (VACV) GLV-1h99,which was constructed to carry the human norepinephrine transporter gene (hNET) under the VACV synthetic early promoter placed at the F14.5L locus for deep-tissue imaging. The hNET protein was expressed at high levels on the membranes of cells infected with this virus. Expression of the hNET protein did not negatively affect virus replication, cytolytic activity in cell culture, or in vivo virother- peutic efficacy. GLV-1h99-mediated expression of the hNET protein in infected cells resulted in specific uptake of the radiotracer (<sup>131</sup>I)-meta-iodobenzylguanidine (MIBG). In mice, GLV-1h99-infected tumors were readily imaged by ( <sup>124</sup>I)-MIBG positron emission tomography. To our knowledge,GLV-1h99 is the first oncolytic virus expressing the hNET protein that can efficiently eliminate tumors and simultaneously allow deep-tissue imaging of infected tumors. © 2009 The Feinstein Institute for Medical Research. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; promoter region; drug efficacy; nonhuman; positron emission tomography; neoplasms; animal cell; mouse; animals; mice; cell line; animal experiment; animal model; gene locus; antineoplastic activity; molecular imaging; cell line, tumor; diagnostic imaging; cell strain cos7; cercopithecus aethiops; pancreas carcinoma; blotting, western; radioactivity; oncolytic virus; (3 iodobenzyl)guanidine i 124; noradrenalin transporter; oncolytic virotherapy; pleura mesothelioma; vaccinia virus; norepinephrine plasma membrane transport proteins; transplantation, heterologous; microscopy, fluorescence; cytolysis; experimental neoplasm; (3 iodobenzyl)guanidine i 131; glv 1h68; glv 1h99; radioisotope; virus recombinant; virus replication; neoplasm transplantation |
| Journal Title: | Molecular Medicine |
| Volume: | 15 |
| Issue: | 5-6 |
| ISSN: | 1076-1551 |
| Publisher: | The Feinstein Institute for Medical Research |
| Date Published: | 2009-05-01 |
| Start Page: | 144 |
| End Page: | 151 |
| Language: | English |
| DOI: | 10.2119/molmed.2009.00014 |
| PUBMED: | 19287510 |
| PROVIDER: | scopus |
| PMCID: | PMC2654849 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: MOMEE" - "Source: Scopus" |
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