NDLI: Inducing antivascular effects in tumors with ultrasound stimulated micron-sized bubbles

Content Provider	IEEE Xplore Digital Library
Author	Matsuura, N. Koonar, E. Siqi Zhu Leung, B. Seo, M. Sivapalan, N. Goertz, D.
Copyright Year	2015
Description	Author affiliation: Sunnybrook Res. Inst., Toronto, ON, Canada (Koonar, E.; Siqi Zhu; Leung, B.; Seo, M.; Sivapalan, N.; Goertz, D.) \|\| Dept. of Med. Imaging, Univ. of Toronto, Toronto, ON, Canada (Matsuura, N.)
Abstract	It has been demonstrated that relatively low intensity ultrasound in combination with microbubbles is capable of inducing a vascular shutdown in preclinical tumor models, and that this can lead to growth inhibition. In previous reports we have shown that this effect can be coupled with anticancer agents to achieve potent antitumor effects, by a means that is not linked to increases in drug uptake. Work to date has been conducted with commercial agents such as Definity or experimental formulations with bubble size distributions designed for resonance at the exposure frequencies employed (0.5-3 MHz). Here we investigate the potential of an experimental agent comprised of micron to submicron sized bubbles to induce antivascular effects in tumors. Experiments were conducted with KHT sarcoma tumors initiated intramuscularly in the hind legs of C3H mice and grown to approximately 200 mm3 in size. Control and treated groups were evaluated (n=5-6/ group), with ultrasound exposures conducted at 1 MHz with a peak negative pressure of 1.6 MPa. This experimental, lipid-encapsulated, perfluorobutane microbubble agent had a volume peak at approximately 1 micron. The agent was injected into mice with injection gas volume fractions matched to Definity doses, and monitored with a Philips L12-5 probe in contrast mode. Tumor tissue was harvested after a pre-sacrifice perfusion stain injection (DiOC7). Agent characterization experiments included frequency dependant attenuation measurements (1-40 MHz) and cavitation detection and analysis. The agent frequency response was such that insonations occurred well below the resonant frequency and exposures were at a level that produced wideband acoustic emissions associated with inertial cavitation. Rapid perfusion reductions were observed in the tumors after treatments as evidenced by perfusion staining and contrast imaging. The particular characteristics of micron-sized formulations may offer advantages in the context of clinical implementations compared to commercial bubbles with larger size distributions.
Starting Page	1
Ending Page	4
File Size	943934
Page Count	4
File Format	PDF
e-ISBN	9781479981823
DOI	10.1109/ULTSYM.2015.0315
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2015-10-21
Publisher Place	Taiwan
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Tumors Ultrasonic imaging Resonant frequency Mice Attenuation Lipidomics antivascular ultrasound microbubbles cancer
Content Type	Text
Resource Type	Article

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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