Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of mice: Comparison between commercially available microbubble contrast agents

被引:99
作者
Wang, XH
Liang, HD
Dong, BW
Lu, QL
Blomley, MJK
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC, Clin Sci Ctr,Muscle Cell Biol Grp, London W12 0NN, England
[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Imaging Sci Dept, London W12 0NN, England
[3] Shanxi Med Univ, Hosp 2, Imaging Sci Dept, Taiyuan, Peoples R China
[4] Bristol Royal Infirm & Gen Hosp, Dept Med Phys & Bioengn, Bristol BS2 8HW, Avon, England
[5] Peoples Liberat Army Gen Hosp, Dept Ultrasound, Beijing, Peoples R China
[6] Carolinas Med Ctr, Neuromuscular ALS Ctr, Charlotte, NC 28203 USA
关键词
D O I
10.1148/radiol.2371040805
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
PURPOSE: To compare three commercial microbubble contrast agents (Optison, SonoVue, and Levovist) for their effect on gene delivery in skeletal muscle in conjunction with the use of therapeutic ultrasound. MATERIALS AND METHODS: The study was approved by the Animal Care and Use Committee. Plasmid DNA (10 mu g) encoding green fluorescent protein (GFP) was mixed with microbubbles (or saline control) and injected into the tibialis anterior muscle of mice with and without adjunct ultrasound (1 MHz, 2 W/cm(2), 30 20% duty cycle). The efficiencies of GFP transgene expression were deterseconds, mined with four experimental conditions: (a) plasmid and saline as control (six mice), (b) plasmid and Optison (six mice), (c) plasmid and SonoVue (four mice), and (d) plasmid and Levovist (air based, four mice). The right legs were exposed to while the left legs were unexposed. Transfection efficiency was assessed ultrasound, by counting the number of GFP-positive fibers. Tissue damage was assessed by measuring the maximal-damage area on serial sections. RESULTS: When ultrasound was applied, both SonoVue and Optison significantly improved (P < .05) gene transfection efficiency. Optison was also effective (P < .05) even when no ultrasound was applied, which is consistent with previous studies. Levovist without ultrasound decreased the level of transfection (P < .05), with increased tissue damage. CONCLUSION: Both non-air-based agents show promise in gene delivery in skeletal muscle with undetectable tissue damage. Enhanced gene transfer with additional ultrasound was achieved only with SonoVue. (c) RSNA, 2005.
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收藏
页码:224 / 229
页数:6
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