Sensitization of Hypoxic Tumors to Radiation Therapy Using Ultrasound-Sensitive Oxygen Microbubbles

International Journal of Radiation Oncology, Biology, Physics
John R EisenbreyMargaret A Wheatley

Abstract

Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment that has been shown to result in both chemotherapy and radiation therapy resistance. The purpose of this study was to use localized microbubble delivery to overcome hypoxia prior to therapy. In this study, surfactant-shelled oxygen microbubbles were fabricated and injected intravenously to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound in mice with human breast cancer tumors. Changes in oxygen and sensitivity to radiation therapy were then measured. In this work, we show that oxygen-filled microbubbles successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline solution or untriggered oxygen microbubbles (P < .001). Using photoacoustic imaging, we also show that oxygen delivery is independent of hemoglobin transport, enabling oxygen delivery to avascular regions of the tumor. Finally, we show that overcoming hypoxia by this method immediately prior to radiation therapy nearly triples radiosensitivity. This improvement in radiosensitivity results in roughly 30 days of improved tumor control, providing statistically...Continue Reading

Citations

Apr 26, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Himanshu ShekharChristy K Holland
May 28, 2019·Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine·Lauren J DelaneyJohn R Eisenbrey
Mar 11, 2020·Frontiers in Oncology·Christoph Reinhold ArnoldUte Ganswindt
Oct 2, 2019·Frontiers in Pharmacology·Sara ZullinoCaterina Guiot
Feb 23, 2020·Frontiers in Pharmacology·Maxime LafondChristy K Holland
Jan 20, 2021·Experimental Biology and Medicine·Madhumithra Subramanian Karthikesh, Xinmai Yang
Feb 7, 2021·Journal of Cancer Research and Clinical Oncology·Chanjuan PengChen Yang
Mar 4, 2021·Ultrasound in Medicine & Biology·Quezia LacerdaJohn R Eisenbrey
Apr 4, 2021·Ultrasound in Medicine & Biology·Gonzalo Collado-LaraNico de Jong
Jun 4, 2021·Acta Biomaterialia·Lauren J DelaneyMargaret A Wheatley
Jun 14, 2021·Advances in Colloid and Interface Science·Marie Pierre Krafft, Jean G Riess
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Jan 31, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Ruyuan SongShuhuai Yao
Mar 5, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Brian E OeffingerMargaret A Wheatley
Aug 29, 2021·Colloids and Surfaces. B, Biointerfaces·Purva B VaidyaMargaret A Wheatley
Nov 19, 2021·Bioconjugate Chemistry·Ayesha ZafarZhifei Dai

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