Department of Radiology, Lucas MRS Research Center, Stanford School of Medicine, Stanford, CA 94305, USA.
Technol Cancer Res Treat. 2011 Apr;10(2):197-210. doi: 10.7785/tcrt.2012.500195.
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 mm(3), the tumours were exposed to five intensities of continuous HIFU (802-1401-2157-3067-4133 W/cm(2)) 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/cm(2), 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/cm(2). 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.
在三种肿瘤模型中，应用不同强度的高强度聚焦超声（HIFU）后，通过 hsp70 启动子控制，研究了荧光素酶活性的体内时间变化。将含有 hsp70 启动子和荧光素酶报告基因的质粒稳定转染至 SCCVII、NIH3T3 和 M21 三种细胞系中，并将肿瘤皮下植入小鼠。当肿瘤大小达到 1300±234mm3 时，将肿瘤用五种强度的连续 HIFU（802-1401-2157-3067-4133W/cm2）照射 20 秒。通过生物发光和磁共振成像来评估组织中的荧光素酶活性和信号强度变化。MRI 扫描方案为预对比和后对比 T1-wt-SE、T2-wt-FSE、DCE-MRI、扩散-wt STEAM 序列、在 1.5-T GE MRI 扫描仪上获得 T2 弛豫时间测定。在 HIFU 强度为 3067W/cm2 时，NIH3T3 肿瘤的荧光素酶活性最高，为 328.1±7.1 倍，在 24 小时时，M21 肿瘤为 3.2±0.6 倍，在 8 小时时，SCCVII 肿瘤为 2.9±0.9 倍，在 2157W/cm2 时，HIFU 后 4 小时。在 SCCVII 肿瘤中，T2 信号强度和 T2 弛豫时间的最大增加为 20.7±3.4%。在 M21 肿瘤中观察到最高的造影剂摄取率为 10.1±1.1%，在 SCCVII 肿瘤中为 14.8±1.9%。在所有肿瘤中，随着 HIFU 强度的增加，扩散系数显著增加，在 SCCVII 肿瘤中最高为 40.3±4.1%。三种稳定转染 hsp70/荧光素酶基因的肿瘤细胞系显示出不同的荧光素酶活性，在 HIFU 应用后不同时间达到峰值，且依赖于肿瘤类型和 HIFU 能量沉积。
