Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model

Feng Yi Yang, Wen Yuan Chang, Wei Ting Lin, Jeng Jong Hwang, Yi Chun Chien, Hsin Ell Wang, Min Lan Tsai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P < 0.05) of glioma cells on day 16 after implantation. Moreover, combining sonication with GCV significantly inhibited tumor growth compared with GCV alone. This study demonstrated that FUS may be used to deliver a wide variety of theranostic agents to the brain for molecular imaging and gene therapy in brain diseases.

Original languageEnglish
Pages (from-to)36260-36268
Number of pages9
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • Blood-brain barrier
  • Brain tumor
  • Focused ultrasound
  • Gene therapy
  • Molecular imaging

ASJC Scopus subject areas

  • Oncology

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