Enhancement of Adenovirus Delivery after Ultrasound-Stimulated Therapy in a Cancer Model

Anna G. Sorace, Jason M. Warram, Marshall Mahoney, Kurt R. Zinn, Kenneth Hoyt

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Improving the efficiency of adenovirus (Ad) delivery to target tissues has the potential to advance the translation of cancer gene therapy. Ultrasound (US)-stimulated therapy uses microbubbles (MBs) exposed to low-intensity US energy to improve localized delivery. We hypothesize that US-stimulated gene therapy can improve Ad infection in a primary prostate tumor through enhanced tumor uptake and retention of the Ad vector. Invitro studies were performed to analyze the degree of Ad infectivity after application of US-stimulated gene therapy. A luciferase-based Ad on a ubiquitous cytomegalovirus (CMV) promoter (Ad5/3-CMV-Luc) was used in an animal model of prostate cancer (bilateral tumor growth) to evaluate Ad transduction efficiency after US-stimulated therapy. Bioluminescence imaging was employed for invivo analysis to quantify Ad infection within the tumor. Invitro studies revealed no difference in Ad transduction between groups receiving US-stimulated therapy using high, low or sham US intensity exposures at various multiplicities of infection (MOIs) (p=0.80). Invivo results indicated that tumors receiving US-stimulated therapy after intra-tumoral injection of Ad5/3-CMV-Luc (1×106 plaque-forming units) exhibited a 95.1% enhancement in tumor delivery compared with control tumors receiving sham US (p=0.03). US-stimulated therapy has significant potential to immediately affect Ad-based cancer gene therapy by improving virus bioavailability in target tissues.

Original languageEnglish (US)
Pages (from-to)2374-2381
Number of pages8
JournalUltrasound in Medicine and Biology
Volume39
Issue number12
DOIs
Publication statusPublished - Jan 1 2013

    Fingerprint

Keywords

  • Adenovirus
  • Cancer
  • Gene therapy
  • Microbubble contrast agent
  • Transduction
  • Ultrasound

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this