Oxygen Microbubbles Improve Radiotherapy Tumor Control in a Rat Fibrosarcoma Model – A Preliminary Study

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  • Fix, Samantha M.
    • Affiliation: Eshelman School of Pharmacy
  • Papadopoulou, Virginie
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
  • Velds, Hunter
    • Other Affiliation: University of Colorado
  • Kasoji, Sandeep K.
    • Affiliation: School of Medicine, Joint Department of Biomedical Engineering, North Carolina State University
  • Rivera, Judith N.
    • Affiliation: School of Medicine, Department of Radiation Oncology
  • Borden, Mark A.
    • Affiliation: School of Medicine, Department of Radiation Oncology
  • Chang, Sha
    • Affiliation: School of Medicine, Joint Department of Biomedical Engineering, North Carolina State University
  • Dayton, Paul A.
    • Affiliation: Eshelman School of Pharmacy
Abstract
  • Cancer affects 39.6% of Americans at some point during their lifetime. Solid tumor microenvironments are characterized by a disorganized, leaky vasculature that promotes regions of low oxygenation (hypoxia). Tumor hypoxia is a key predictor of poor treatment outcome for all radiotherapy (RT), chemotherapy and surgery procedures, and is a hallmark of metastatic potential. In particular, the radiation therapy dose needed to achieve the same tumor control probability in hypoxic tissue as in normoxic tissue can be up to 3 times higher. Even very small tumors (<2–3 mm3) comprise 10–30% of hypoxic regions in the form of chronic and/or transient hypoxia fluctuating over the course of seconds to days. We investigate the potential of recently developed lipid-stabilized oxygen microbubbles (OMBs) to improve the therapeutic ratio of RT. OMBs, but not nitrogen microbubbles (NMBs), are shown to significantly increase dissolved oxygen content when added to water in vitro and increase tumor oxygen levels in vivo in a rat fibrosarcoma model. Tumor control is significantly improved with OMB but not NMB intra-tumoral injections immediately prior to RT treatment and effect size is shown to depend on initial tumor volume on RT treatment day, as expected.
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  • Article
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  • In Copyright
Journal title
  • PLoS ONE
Journal volume
  • 13
Journal issue
  • 4
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  • English
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  • National Institutes of Health
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  • Eshelman Institute for Innovation, UNC-CH; Carolina Center of Cancer Nanotechnology Excellence, UNC-CH; Office of Naval Research
Date uploaded
  • January 3, 2019

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