Miller Douglas L, Song Jianming
Department of Radiology, University of Michigan Medical Center, Ann Arbor, MI 48109-0553, USA.
Ultrasound Med Biol. 2003 Jun;29(6):887-93. doi: 10.1016/s0301-5629(03)00031-0.
The potential application of high-intensity focused ultrasound (US), HIFU, was investigated for nonthermal gene transfer and tumor ablation. Renal carcinoma (RENCA) tumors were implanted on the hind leg of BALB/c mice and injected with a marker plasmid. Optison US contrast agent was also injected into the tumor (IT) or into the venous (IV) circulation. HIFU at 1.55 MHz was applied to the tumors with guidance from diagnostic US images. One test of transfection was also performed with lithotripter shock waves. In one set of exposures, tumor volume was followed for 4 days and a beta-galactosidase marker plasmid was used for localization of transfected cells. A second set of exposures employed a luciferase marker plasmid for assessing overall transfection after 2 days. Use of 100-ms bursts at 8-MPa peak rarefactional pressure amplitude stopped tumor growth during the 4-day period, compared to a 2.8-fold growth in shams and yielded luciferase expression 34-fold greater than in shams. Longer bursts or higher pressure amplitudes led to decreases in tumor growth, but did not yield increases in transfection. The HIFU results were similar to those of shock waves for cavitation enhanced by IT Optison. These results should aid in optimizing the application of HIFU for nonthermal tumor treatment.
研究了高强度聚焦超声（HIFU）在非热基因转移和肿瘤消融方面的潜在应用。将肾癌细胞（RENCA）肿瘤接种到BALB/c小鼠的后腿上，并注射标记质粒。同时将Optison超声造影剂注入肿瘤内（IT）或静脉循环（IV）中。在诊断性超声图像引导下，将1.55MHz的HIFU应用于肿瘤。还用碎石机冲击波进行了一次转染测试。在一组照射中，跟踪肿瘤体积4天，并使用β-半乳糖苷酶标记质粒来定位转染细胞。第二组照射使用荧光素酶标记质粒来评估2天后的总体转染情况。在4天期间，使用峰值稀疏压力振幅为8MPa的100ms脉冲可使肿瘤生长停止，而假手术组肿瘤生长了2.8倍，且荧光素酶表达比假手术组高34倍。更长的脉冲或更高的压力振幅会导致肿瘤生长减缓，但不会使转染增加。HIFU的结果与通过肿瘤内注入Optison增强空化作用的冲击波的结果相似。这些结果应有助于优化HIFU在非热肿瘤治疗中的应用。
