| Autor: |
Fix SM; Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America., Papadopoulou V; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and NC State University, Chapel Hill, NC, United States of America., Velds H; Department of Mechanical Engineering, University of Colorado, Boulder, Colorado, United States of America., Kasoji SK; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and NC State University, Chapel Hill, NC, United States of America., Rivera JN; Department of Radiation Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America., Borden MA; Department of Radiation Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America., Chang S; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and NC State University, Chapel Hill, NC, United States of America.; Department of Radiation Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America., Dayton PA; Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and NC State University, Chapel Hill, NC, United States of America. |
| Abstrakt: |
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. |
