The in vivo temporal changes of luciferase activity were investigated under the control of an hsp70 promoter in three tumour models after the application of different intensities of high-intensity focused ultrasound (HIFU). Three cell lines, SCCVII, NIH3T3 and M21 were stably transfected with a plasmid containing the hsp70 promoter and luciferase reporter gene, and tumours were subcutaneously initiated into mice. At a size of 1300 ± 234 mm³, the tumours were exposed to five intensities of continuous HIFU (802-1401-2157-3067-4133 W/cm2) for 20 sec. Bioluminescence and MR imaging were performed to assess luciferase activity and signal intensity changes in the tissue. The MRI scan protocol was pre- and post-contrast T1-wt-SE, T2-wt-FSE, DCE-MRI, diffusion-wt STEAM sequence, T2 relaxation time determination obtained on a 1.5-T GE MRI scanner. The NIH3T3 tumours showed the highest luciferase activity of 328.1 ± 7.1 fold at 24 h at a HIFU intensity of 3067 W/cm², the M21 tumours of 3.2 ± 0.6 fold 8 hours and the SCCVII tumours 2.9 ± 0.9 fold 4 hours post-HIFU at 2157 W/cm². The greatest increase in T2 signal intensity and T2 relaxation time of 20.7 ± 3.4% was seen in the SCCVII tumours. The highest contrast medium uptake of 10.1 ± 1.1% was noted in the M21 tumours, and 14.8 ± 1.9% in the SCCVII tumours. In all tumours, a significant increase in the diffusion coefficient was seen with increased HIFU intensity, the highest of which was 40.3 ± 4.1% in the SCCVII tumours. The three tumour cell lines stably transfected with the hsp70/luciferase gene showed differential luciferase activity, which peaked at different times after the application of HIFU and was dependant on tumour type and HIFU energy deposition.

Key words: Tumour cell lines; Thermal stress; hsp70 expression; Bioluminescence imaging; MR imaging; Focused ultrasound.

This article can be cited as:
Hundt, W., Steinbach, S., Burbelko, M., Kiessling, A., Rominger, M., O’Connell-Rodwell, C. E., Mayer, D., Bednarski, M.D., Guccione, S. Induction of Luciferase Activity under the Control of an hsp70 Promoter Using High-Intensity Focused Ultrasound: Combination of Bioluminescence and MRI Imaging in Three Different Tumour ModelsTechnol Cancer Res Treat. 10, 197-210 (2011).