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

Amber Miller, Lukkana Suksanpaisan, Shruthi Naik, Rebecca Nace, Mark J Federspiel, Kah-Whye Peng, Stephen J Russell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number14005
JournalMolecular Therapy - Oncolytics
Volume1
DOIs
StatePublished - Dec 10 2014

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Oncolytic Viruses
Reporter Genes
Viruses
Infection
Neoplasms
Tomography
Oncogenic Viruses
Vesicular Stomatitis
Chromosome Mapping
Photons
Virion
Thyroid Gland

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology
  • Pharmacology (medical)

Cite this

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 J; Peng, Kah-Whye; Russell, Stephen J.

In: Molecular Therapy - Oncolytics, Vol. 1, 14005, 10.12.2014.

Research output: Contribution to journalArticle

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