Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy

Systemically administered oncolytic viruses have the ability to cause tumor destruction through the expansion and coalescence of intratumoral infectious centers. Efficacy is therefore dependent upon both the density and intratumoral distribution of virus-infected cells achieved after initial virus i...

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Main Authors:	Miller, Amber, Suksanpaisan, Lukkana, Naik, Shruthi, Nace, Rebecca, Federspiel, Mark, Peng, Kah Whye, Russell, Stephen J
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782940/

id	pubmed-4782940
recordtype	oai_dc
spelling	pubmed-47829402016-04-26 Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy Miller, Amber Suksanpaisan, Lukkana Naik, Shruthi Nace, Rebecca Federspiel, Mark Peng, Kah Whye Russell, Stephen J Article Systemically administered oncolytic viruses have the ability to cause tumor destruction through the expansion and coalescence of intratumoral infectious centers. Efficacy is therefore dependent upon both the density and intratumoral distribution of virus-infected cells achieved after initial virus infusion, and delivery methods are being developed to enhance these critical parameters. However, the three-dimensional (3D) mapping of intratumoral infectious centers is difficult using conventional immunohistochemical methodology, requiring painstaking 3D reconstruction of numerous sequential stained tumor sections, with no ability to study the temporal evolution of spreading infection in a single animal. We therefore developed a system using very high-resolution noninvasive in vivo micro single-photon emitted computed tomography/computed tomography (microSPECT/CT) imaging to determine the intratumoral distribution of thyroid radiotracers in tumors infected with an oncolytic virus encoding the thyroidal sodium–iodide symporter (NIS). This imaging system was used for longitudinal analysis of the density, distribution, and evolution of intratumoral infectious centers after systemic administration of oncolytic vesicular stomatitis virus in tumor-bearing mice and revealed heterogeneous delivery of virus particles both within and between tumors in animals receiving identical therapy. This study provides compelling validation of high resolution in vivo reporter gene mapping as a convenient method for serial monitoring of intratumoral virus spread that will be necessary to address critical barriers to systemic oncolytic virus efficacy such as intratumoral delivery. Nature Publishing Group 2014-12-10 /pmc/articles/PMC4782940/ /pubmed/27119095 http://dx.doi.org/10.1038/mto.2014.5 Text en Copyright © 2014 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Miller, Amber Suksanpaisan, Lukkana Naik, Shruthi Nace, Rebecca Federspiel, Mark Peng, Kah Whye Russell, Stephen J
spellingShingle	Miller, Amber Suksanpaisan, Lukkana Naik, Shruthi Nace, Rebecca Federspiel, Mark Peng, Kah Whye Russell, Stephen J Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
author_facet	Miller, Amber Suksanpaisan, Lukkana Naik, Shruthi Nace, Rebecca Federspiel, Mark Peng, Kah Whye Russell, Stephen J
author_sort	Miller, Amber
title	Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
title_short	Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
title_full	Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
title_fullStr	Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
title_full_unstemmed	Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
title_sort	reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy
description	Systemically administered oncolytic viruses have the ability to cause tumor destruction through the expansion and coalescence of intratumoral infectious centers. Efficacy is therefore dependent upon both the density and intratumoral distribution of virus-infected cells achieved after initial virus infusion, and delivery methods are being developed to enhance these critical parameters. However, the three-dimensional (3D) mapping of intratumoral infectious centers is difficult using conventional immunohistochemical methodology, requiring painstaking 3D reconstruction of numerous sequential stained tumor sections, with no ability to study the temporal evolution of spreading infection in a single animal. We therefore developed a system using very high-resolution noninvasive in vivo micro single-photon emitted computed tomography/computed tomography (microSPECT/CT) imaging to determine the intratumoral distribution of thyroid radiotracers in tumors infected with an oncolytic virus encoding the thyroidal sodium–iodide symporter (NIS). This imaging system was used for longitudinal analysis of the density, distribution, and evolution of intratumoral infectious centers after systemic administration of oncolytic vesicular stomatitis virus in tumor-bearing mice and revealed heterogeneous delivery of virus particles both within and between tumors in animals receiving identical therapy. This study provides compelling validation of high resolution in vivo reporter gene mapping as a convenient method for serial monitoring of intratumoral virus spread that will be necessary to address critical barriers to systemic oncolytic virus efficacy such as intratumoral delivery.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782940/
_version_	1613548956527099904

Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy

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