Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: Study in a murine model
Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: Study in a murine model
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DOI：
10.1148/radiol.2342030889
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发表时间：
2005-02-01
期刊：
影响因子：
19.7
通讯作者：
Li, KCP
中科院分区：
文献类型：
--
作者：
Yuh, EL;Shulman, SG;Li, KCP
目得：为了定量确定全身脂质体阿霉素治疗的肿瘤与脉冲高强度聚焦超声和研究的机制，这种交付在小鼠model.MATERIALS和METHODS：所有的动物工作进行了符合指导方针和机构动物护理委员会的批准。C3 H小鼠在侧腹接受SCC 7（一种鼠鳞状细胞癌细胞系）的α-细胞悬浮液的皮下注射;药物递送研究中的小鼠（n = 32）接受单侧注射，而机制研究中的小鼠（n = 10）接受双侧注射。当肿瘤体积达到1 cm（3）时进行治疗。在药物递送研究中，将盐酸多柔比星脂质体注射到尾静脉中：小鼠接受多柔比星注射和高强度聚焦超声治疗，单独注射多柔比星，或两种形式的治疗（对照）。切除肿瘤，用荧光分光光度法测定阿霉素含量。在机制研究中，所有小鼠均接受500 kDa右旋糖酐-异硫氰酸荧光素注射到尾静脉中，其中一半在注射前暴露于高强度聚焦超声。两侧肿瘤作为每组的对照。异硫氰酸右旋糖酐荧光素外渗观察通过使用在体内共聚焦microscopics.Results：平均阿霉素浓度与脉冲高强度聚焦超声治疗的肿瘤为9.4 μ g。g（-1）+/- 2.1（标准差），并且显著更高（124% [9.4 μ g. g（-1）/4.2 μ g。g（-1）]）比未接受高强度聚焦超声治疗的患者（4.2 μ g. g（-1）+/- 0.95）（P
PURPOSE: To quantitatively determine the delivery of systemic liposomal doxorubicin to tumors treated with pulsed high-intensity focused ultrasound and to study the mechanism underlying this delivery in a murine model.MATERIALS AND METHODS: All animal work was performed in compliance with guidelines and approval of institutional animal care committee. C3H mice received subcutaneous injections in the flank of a-cell suspension of SCC7, a murine squamous cell carcinoma cell line; mice (n = 32) in drug delivery study received unilateral injections, whereas mice (n = 10) in mechanistic study received bilateral injections. Tumors were treated when they reached 1 cm(3) in volume. In the drug delivery study, doxorubicin hydrochloride liposomes were injected into the tail vein: Mice received therapy with doxorubicin injections and high-intensity focused ultrasound, doxorubicin injections alone, or neither form of therapy (controls). Tumors were removed, and the,doxorubicin content was assayed with fluorescent spectrophotometry. In the mechanistic study, all mice received an injection of 500-kDa dextran-fluorescein isothyocyanate into the tail vein, and half of them were exposed to high-intensity focused ultrasound prior to injection. Contralateral tumors served as controls for each group. Extravasation of dextranfluorescein isothyocyanate was observed by using in vivo confocal microscopy.RESULTS: Mean doxorubicin concentration in tumors treated with pulsed high-intensity focused ultrasound was 9.4 mug . g(-1) +/- 2.1 (standard deviation), and it was significantly higher (124% [9.4 mug . g(-1)/4.2 mug . g(-1)]) than in those that were not treated with high-intensity focused ultrasound (4.2 mug . g(-1) +/- 0.95) (P