Gene Transfer with Echo-enhanced Contrast Agents: Comparison between Albunex, Optison, and Levovist in Mice—Initial Results

Li, Tieli; Tachibana, Katsuro; Kuroki, Motomu; Kuroki, Masahide

doi:10.1148/radiol.2292020500

Cited by 214 publications

(132 citation statements)

References 30 publications

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“…However, some mice died immediately after receiving an intra-TV injection of Optison even without the sonoporation. Although Optison has been shown to be a useful agent for ultrasound-based transfection in rats and larger animals [9,[12][13][14]17,18], BR14 may be more suitable in mice because a TV injection of BR14 did not kill any mice in the present study. The difference in results may be due to difference in the size of the agents: the mean diameter of BR14 is 2.5-3.0 lm, which is small compared with its predecessors [17,35,36].…”

Section: Discussionmentioning

confidence: 60%

“…The extent of cavitation bubble formation and subsequent increase in membrane permeability can be enhanced by use of microbubble echo contrast agents. This method has been applied to skeletal muscle of mice [9], as well as myocardium of both rats [10] and dogs [11], in vivo, using various microbubble agents including Levovist, Hexabrix, and Optison [9][10][11][12][13][14][15][16][17][18]. It has been indicated that the transfection efficiency is dependent on both the ultrasound parameters and the formulation of microbubbles.…”

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confidence: 99%

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Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart

Tsunoda

Mazda

Oda

et al. 2005

Biochemical and Biophysical Research Communications

129

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Naked plasmid DNA (pDNA) and short interfering RNA (siRNA) duplexes were transduced into adult murine heart by means of sonoporation using the third-generation microbubble, BR14. Plasmid DNAs carrying luciferase, b-galactosidase (b-gal), or enhanced green fluorescent protein (EGFP) reporter genes were mixed with BR14 and injected percutaneously into the left ventricular (LV) cavity of C57BL/6 mice while exposed to transthoracic ultrasound at 1 MHz for 60 s. Sonoporation at an output intensity of 2.0 W/cm 2 and a 50% pulse duty ratio resulted in the highest luciferase expression in the heart. Histological examinations revealed significant expression of the b-gal and EGFP reporters in the subendocardial myocardium of LV. Intraventricular co-injection of siRNA-GFP and BR14 with concomitant ultrasonic exposure resulted in substantial reduction in EGFP expression in the coronary artery in EGFP transgenic mice. The present method may be applicable to gain-of-function and loss-of-function genetic engineering in vivo of adult murine heart.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart

Tsunoda

Mazda

Oda

et al. 2005

Biochemical and Biophysical Research Communications

129

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“…25 When compared to similar available agents, Optison was superior for US-mediated gene transfer to skeletal muscle in vivo. 26 A recent study also demonstrated that the effects of US on the cell membrane are much more profound in the presence of Optison, providing further support for the role of cavitation. 27 Thus, we have tested, for the first time, the effect of sonoporation on nonviral gene transfer to the lung.…”

Section: Introductionmentioning

confidence: 86%

Use of ultrasound to enhance nonviral lung gene transfer in vivo

et al. 2007

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We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents. US exposure did not increase GL67/ pDNA or PEI/pDNA gene transfer compared to Optisontreated animals. However, it increased naked pDNA transfection efficiency by approximately 15-fold compared to Optison-treated animals, suggesting that despite ultrasound being attenuated by air in the lung, sufficient energy penetrates the tissue to increase gene transfer. US-induced lung haemorrhage, assessed histologically, increased with prolonged US exposure. The left lung was more affected than the right and this was mirrored by a lesser increase in naked pDNA gene transfer, in the left lung. The positive effect of US was dependent on Optison, as in its absence US did not increase naked pDNA transfection efficiency. We have thus established proof of principle that US can increase nonviral gene transfer, in the air-filled murine lung.

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“…Alternative clinical echo-contrast agents are now available in Japan. Levovist is one of these agents, although its gene transduction efficacy is reported to be inferior to that of Optison (27). Both are classified as second-generation microbubble agents.…”

Section: Discussionmentioning

confidence: 99%

Microbubble‐enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen‐induced arthritis

Nakaya

Shimizu

Isobe

et al. 2005

Arthritis & Rheumatism

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Objective. To evaluate whether microbubbleenhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model.Methods. Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX؉/US؉ group), while the left knees were not (MTX؉/US؊ group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin-1␤ (IL-1␤) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble-enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28.Results. The MTX concentration in synovial tissue was significantly higher in the MTX؉/US؉ group than in the MTX؉/US؊ group. Synovial inflammation was less prominent in the MTX؉/US؉ group compared with the MTX؉/US؊ group, judging from the results of the histologic evaluation and the gene expression levels of IL-1␤ in synovial tissue. It also appeared that microbubble-enhanced US exposure itself did not affect inflammation.Conclusion. Microbubble-enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.

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Gene Transfer with Echo-enhanced Contrast Agents: Comparison between Albunex, Optison, and Levovist in Mice—Initial Results

Abstract: Low-intensity ultrasound with echo-enhanced Optison induced efficient gene transfer unlike that with Albunex or Levovist.

Cited by 214 publications

References 30 publications

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart

Use of ultrasound to enhance nonviral lung gene transfer in vivo

Microbubble‐enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen‐induced arthritis

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