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Sensitization of Hypoxic Tumors to Radiation Therapy Using Ultrasound-Sensitive Oxygen Microbubbles
Journal article   Open access

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

John R Eisenbrey, Rawan Shraim, Ji-Bin Liu, Jingzhi Li, Maria Stanczak, Brian Oeffinger, Dennis B Leeper, Scott W Keith, Lauren J Jablonowski, Flemming Forsberg, …
International journal of radiation oncology, biology, physics, v 101(1), pp 88-96
01 May 2018
DOI: https://doi.org/10.1016/j.ijrobp.2018.01.042
PMID: 29477294
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5886808View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Cell Line, Tumor Female Humans Injections, Intravenous Mice Mice, Nude Microbubbles Oxygen - administration & dosage Oxygen - metabolism Oxygen Consumption Partial Pressure Radiation Tolerance Random Allocation Triple Negative Breast Neoplasms - diagnostic imaging Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology Triple Negative Breast Neoplasms - radiotherapy Tumor Hypoxia - radiation effects Tumor Microenvironment Ultrasonic Therapy - methods
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 significant improvements in tumor growth and animal survival (P < .03). Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.

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90 citations in Web of Science
94 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Oncology
Radiology, Nuclear Medicine & Medical Imaging
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