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 virotherpeutic efficacy. GLV-1h99-mediated expression of the hNET protein in infected cells resulted in specific uptake of the radiotracer [131I]-meta-iodobenzylguanidine (MIBG). In mice, GLV-1h99-infected tumors were readily imaged by [124I]-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.

• Authors: Nanhai Chen, Qian Zhang, Yong A Yu, Jochen Stritzker, Peter Brader, Andreas Schirbel, Samuel Samnick, Inna Serganova, Ronald Blasberg, Yuman Fong, Aladar A Szalay
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) 2009 May-Jun Vol. 15 Issue 5-6 Pg. 144-51 ISSN: 1528-3658 [Electronic] England
• PMID: 19287510 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Norepinephrine Plasma Membrane Transport Proteins

Topics

• Animals
• Blotting, Western
• Cell Line
• Cell Line, Tumor
• Chlorocebus aethiops
• Diagnostic Imaging (methods)
• Humans
• Mice
• Microscopy, Fluorescence
• Neoplasm Transplantation
• Neoplasms (pathology, therapy)
• Norepinephrine Plasma Membrane Transport Proteins (genetics, metabolism)
• Oncolytic Virotherapy (methods)
• Transplantation, Heterologous
• Vaccinia virus (genetics, metabolism, physiology)