Perfusion pressure is a critical determinant of the intratumoral extravasation of oncolytic viruses

Amber Miller, Rebecca Nace, Camilo C. Ayala-Breton, Michael Steele, Kent R Bailey, Kah-Whye Peng, Stephen J Russell

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Antitumor efficacy of oncolytic virotherapy is determined by the density and distribution of infectious centers within the tumor, which may be heavily influenced by the permeability and blood flow in tumor microvessels. Here, we investigated whether systemic perfusion pressure, a key driver of tumor blood flow, could influence the intratumoral extravasation of systemically administered oncolytic vesicular stomatitis virus (VSV) in myeloma tumor-bearing mice. Exercise was used to increase mean arterial pressure, and general anesthesia to decrease it. A recombinant VSV expressing the sodium iodide symporter (NIS), which concentrates radiotracers at sites of infection, was administered intravenously to exercising or anesthetized mice, and nuclear NIS reporter gene imaging was used to noninvasively track the density and spatial distribution of intratumoral infectious centers. Anesthesia resulted in decreased intratumoral infection density, while exercise increased the density and uniformity of infectious centers. Perfusion state also had a significant impact on the antitumor efficacy of the VSV therapy. In conclusion, quantitative dynamic radiohistologic imaging was used to noninvasively interrogate delivery of oncolytic virotherapy, highlighting the critical importance of perfusion pressure as a driver of intratumoral delivery and efficacy of oncolytic viruses.

Original languageEnglish (US)
Pages (from-to)306-317
Number of pages12
JournalMolecular Therapy
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Oncolytic Viruses
Vesicular Stomatitis
Oncolytic Virotherapy
Perfusion
Pressure
Viruses
Neoplasms
Microvessels
Infection
Reporter Genes
General Anesthesia
Permeability
Arterial Pressure
Anesthesia

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Perfusion pressure is a critical determinant of the intratumoral extravasation of oncolytic viruses. / Miller, Amber; Nace, Rebecca; Ayala-Breton, Camilo C.; Steele, Michael; Bailey, Kent R; Peng, Kah-Whye; Russell, Stephen J.

In: Molecular Therapy, Vol. 24, No. 2, 01.02.2016, p. 306-317.

Research output: Contribution to journalArticle

Miller, Amber ; Nace, Rebecca ; Ayala-Breton, Camilo C. ; Steele, Michael ; Bailey, Kent R ; Peng, Kah-Whye ; Russell, Stephen J. / Perfusion pressure is a critical determinant of the intratumoral extravasation of oncolytic viruses. In: Molecular Therapy. 2016 ; Vol. 24, No. 2. pp. 306-317.
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