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Open Access Research

Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

Dana Haddad12, Nanhai G Chen3, Qian Zhang3, Chun-Hao Chen2, Yong A Yu3, Lorena Gonzalez2, Susanne G Carpenter2, Joshua Carson2, Joyce Au2, Arjun Mittra2, Mithat Gonen2, Pat B Zanzonico4, Yuman Fong2* and Aladar A Szalay135*

Author Affiliations

1 Department of Biochemistry, University of Wuerzburg, Wuerzburg, D-97074, Germany

2 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA

3 Genelux Corporation, San Diego Science Center, San Diego, CA 92109, USA

4 Departments of Medical Physics and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA

5 Department of Radiation Oncology, University of California San Diego, San Diego, CA 92093, USA

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Journal of Translational Medicine 2011, 9:36  doi:10.1186/1479-5876-9-36

Published: 31 March 2011

Abstract

Introduction

Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153.

Methods

GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free 124I radiotracer.

Results

GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via 124I-PET.

Conclusion

Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.