AVS 60th International Symposium and Exhibition
    Biomaterial Interfaces Tuesday Sessions
       Session BI-TuP

Paper BI-TuP3
Ultrasound Imaging, Gamma Scintigraphy and HIFU Therapy with Perfluorocarbon Loaded Iron-Silica Nanoshells

Tuesday, October 29, 2013, 6:00 pm, Room Hall B

Session: Biomaterials Interfaces Poster Session
Presenter: A. Liberman, University of California San Diego
Authors: A. Liberman, University of California San Diego
Z. Wu, University of California San Diego
C. Barback, University of California San Diego
R. Viveros, University of California San Diego
S.L. Blair, University of California San Diego
D. Vera, University of California San Diego
L.G. Ellies, University of California San Diego
R.F. Mattrey, University of California San Diego
W.C. Trogler, University of California San Diego
A.C. Kummel, University of California San Diego
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The reported positive margin rate from wire localized excisions of breast cancers is approximately 20-50%; however, by preoperatively injecting a radioactive seed into the tumor under CT guidance, the excision rate is halved because the surgeon can constantly reorient the dissection to place the seed in the center of the specimen. Unfortunately, radioactive seed localization has several safety challenges, only single focus can be localized, and incisions are required to implant the seeds, so it is rarely employed. As an alternative, gas-filled hollow Fe-doped silica particles have been developed, which can be used for ultrasound-guided surgery even for multiple foci. The function of the Fe doping is to render the silica shells biodegradable. The particles are synthesized through a sol-gel method on a polystyrene template, and calcined to create hollow, rigid nanoshells. The Fe-doped silica shell is derived from tetramethyl orthosilicate and iron ethoxide, which forms a rigid, nanoporous shell upon calcination. The nanoshells are filled with perfluoropentane vapor or liquid. The flourous phase is contained within the shell due to its extremely low solubility in water. In vivo particle longevity studies have been performed in tumor bearing mouse models show signal presence up to 10 days post injection. To study biodistribution, nanoshells were functionalized with DTPA and radiolabeled with 111In and then imaged by γ-scintigraphy. Scintigraphic imaging and γ-counting confirm that particles undergoing IV delivery to tumor bearing mice will passively accumulate in the tumors which may allow for tumor detection and therapuetic applications. The nanoshells break under acoustic excitation to release gas pockets which increase acoustic energy absorption and reduce acoustic cavitation threshold. Therefore they may also be employed as a sensitizing agent in high intensity focused ultrasound (HIFU) therapy. Traditional ultrasound agents which can be used as a HIFU senstizing agent pose several potential drawbacks such as poor in vivo persistence (mins) and high risk during continuous perfusion. Preliminary in vivo HIFU ablation studies show that few particles are needed in order to develop a sensitizing effect to HIFU thereby substantially reduce the amount of HIFU exposure necessary to achieve an ablative effect. It was found that nanoshells systemically adminstered to breast tumor bearing mice could be cavitated by HIFU 24 hrs after administration. This cavitation caused liquification within the focal volume of the HIFU which contained the nanoshells within seconds. This may potentially allow for a larger area to be ablated in less time with less power.