# Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $139,283

## Abstract

PROJECT SUMMARY
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. In fact, tumor
hypoxia is a key predictor of poor treatment outcome for all radiotherapy, chemotherapy and surgery procedures,
as well as a hallmark of metastatic potential. In particular, tumor cell resistance to radiotherapy is 3 fold increased
in anoxic cells and even very small tumors comprise 10-30% of hypoxic regions in the form of chronic and/or
transient hypoxia fluctuating over course of seconds to days. Recently, lipid-stabilized oxygen microbubbles
(OMBs) have been used in vivo to relieve tumor hypoxia in sonodynamic therapy when injected directly in the
tumors, as well as shown to sustain asphyxiated animals for over two hours when injected intra-peritoneally. Our
preliminary data supports our hypothesis that oxygen microbubbles could also be used to relieve tumor hypoxia
during radiotherapy and significantly improve treatment outcome. In addition, there has been no systemic OMB
delivery demonstration to date for tumor hypoxia modulation with OMBs, due in part to the difficulty of measuring
hypoxia in vivo reliably in combination with these administrations. We hypothesize that we can guide specially
formulated OMBs via ultrasound imaging, and preferentially release oxygen, in the tumor for radiosensitization
to significantly improve the radiotherapy therapeutic ratio. In order to test our hypothesis, will optimize
microbubble formulations and administration parameters, evaluate biological mechanisms and kinetics, and
validate our hypothesis both in a rodent model and then in a translational large animal model across two of the
leading veterinary schools in the country. To achieve these goals, we approach this project with a collaborative
team of leading experts in the fields of microbubbles, oxygen transport, radiation oncology, and tumor biology.

## Key facts

- **NIH application ID:** 10163814
- **Project number:** 5R01CA232148-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Paul A Dayton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $139,283
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163814

## Citation

> US National Institutes of Health, RePORTER application 10163814, Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy (5R01CA232148-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163814. Licensed CC0.

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