High Intensity Focused Ultrasound induced Gene Activation in Solid Tumors

Abstract

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 (3rd 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.