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Evaluation of pulsed high intensity focused ultrasound exposures on metastasis in a murine model

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Abstract

High intensity focused ultrasound (HIFU) may be employed in two ways: continuous exposures for thermal ablation of tissue (>60°C), and pulsed-exposures for non-ablative effects, including low temperature hyperthermia (37–45°C), and non thermal effects (e.g. acoustic cavitation and radiation forces). Pulsed-HIFU effects may enhance the tissue’s permeability for improved delivery of drugs and genes, for example, by opening up gaps between cells in the vasculature and parenchyma. Inducing these effects may improve local targeting of therapeutic agents, however; concerns exist that pulsed exposures could theoretically also facilitate dissemination of tumor cells and exacerbate metastases. In the present study, the influence of pulsed-HIFU exposures on increasing metastatic burden was evaluated in a murine model with metastatic breast cancer. A preliminary study was carried out to validate the model and determine optimal timing for treatment and growth of lung metastases. Next, the effect of pulsed-HIFU on the metastatic burden was evaluated using quantitative image processing of whole-lung histological sections. Compared to untreated controls (2/15), a greater number of mice treated with pulsed-HIFU were found to have lungs “overgrown” with metastases (7/15), where individual metastases grew together such that they could not accurately be counted. Furthermore, area fraction of lung metastases (area of metastases/area of lungs) was ~30% greater in mice treated with pulsed-HIFU; however, these differences were not statistically significant. The present study details the development of an animal model for investigating the influence of interventional techniques or exposures (such as pulsed HIFU) on metastatic burden.

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Acknowledgments

We would like to thank Dr Arnulfo Mendoza and Ms. Mary Angstadt for their technical assistance, and Dr Marius Linguraru for helpful consultations on image processing. This study was supported in part by Howard Hughes Medical Institute NIH Research Scholars Program (J.S.), and by the intramural research program of the NIH Clinical Center.

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Authors and Affiliations

  1. Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA

    Hilary Hancock, Matthew R. Dreher, Jennifer Shih, Bradford J. Wood & Victor Frenkel

  2. Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA

    Nigel Crawford, Claire B. Pollock & Kent Hunter

  3. Molecular Imaging Lab, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Building 10, Room 1N306a, 10 Center Drive, Bethesda, MD, 20892, USA

    Victor Frenkel

Authors
  1. Hilary Hancock
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  2. Matthew R. Dreher
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  3. Nigel Crawford
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  4. Claire B. Pollock
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  5. Jennifer Shih
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  6. Bradford J. Wood
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  7. Kent Hunter
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  8. Victor Frenkel
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Correspondence to Victor Frenkel.

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Hancock, H., Dreher, M.R., Crawford, N. et al. Evaluation of pulsed high intensity focused ultrasound exposures on metastasis in a murine model. Clin Exp Metastasis 26, 729–738 (2009). https://doi.org/10.1007/s10585-009-9272-9

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  • DOI: https://doi.org/10.1007/s10585-009-9272-9

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