High intensity focused ultrasound induced gene activation in solid tumors

Journal Article

In this work, the feasibility of using high intensity focused ultrasound (HIFU) to activate trans-gene expression in a mouse tumor model was investigated. 4T1 cancer cells were implanted subcutaneously in the hind limbs of Balb/C mice and adenovirus luciferase gene vectors under the control of heat shock protein 70B promoter (Adeno-hsp70B-Luc) were injected intratumoraly for gene transfection. One day following the virus injection, the transfected tumors were heated to a peak temperature of 55, 65, 75, and 85°C, respectively, in 10s at multiple sites around the center of the tumor using a HIFU transducer operated at either 1.1-MHz (fundamental) or 3.3-MHz (3 rd harmonic) frequency. Inducible luciferase gene expression was found to vary from 15-fold to 120-fold of the control group following 1.1-MHz HIFU exposure. The maximum gene activation was produced at a peak temperature of 65∼75°C one day following HIFU exposure and decayed gradually to baseline level within 7 days. The inducible gene activation produced by 3.3-MHz HIFU exposure (75°C-10s) was found to be comparable to that produced by hyperthermia (42°C-30min). Altogether, these results demonstrate the feasibility of using HIFU as a simple and versatile physical means to regulate trans-gene expression in vivo. This unique feature may be explored in the future for a synergistic combination of HIFU-induced thermal ablation with heat-induced gene therapy for improved cancer therapy. © 2006 American Institute of Physics.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Kon, T; Li, C; Zhong, P

Published Date

  • May 8, 2006

Published In

Volume / Issue

  • 829 /

Start / End Page

  • 588 - 592

Electronic International Standard Serial Number (EISSN)

  • 1551-7616

International Standard Serial Number (ISSN)

  • 0094-243X

Digital Object Identifier (DOI)

  • 10.1063/1.2205542

Citation Source

  • Scopus