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Oxygen Microbubbles Transiently Relieve Tumor Hypoxia and May Improve Radiation Therapy Tumor Control

S Chang1,3*, S Fix2 , V Papadopoulou3 , H Velds4 , S Kasoji3 , J Rivera3 , M Borden4 , P Dayton3 , (1) School of Medicine, University of North Carolina, Chapel Hill, NC, (2) Eshlman School of Pharmacy, University of North Carolina, Chapel Hill, NC, (3) Biomedical Enginnering, University of North Carolina, Chapel Hill, NC, (4) University of Calorado Boulder, Boulder, CO,


(Tuesday, 7/31/2018) 1:45 PM - 3:45 PM

Room: Karl Dean Ballroom A1

Purpose: 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 radiotherapy (RT) and is a hallmark of metastatic potential. The radiation dose needed to achieve a given tumor control in a hypoxic environment can be up to 3 times higher than in a well-oxygenated environment. There have been many attempts to reoxygenate tumors, including hyperbaric oxygenation, inhaled carbogen, nitroimidazoles and other radiosensitizers. Practical administration difficulties, vasoconstriction and normal tissue toxicity, however, have severely limited their clinical translation. In this study we investigate the potential of recently developed lipid-stabilized oxygen microbubbles to decrease tumor hypoxia during RT and thus increase tumor control without added toxicity.

Methods: Female Fisher 344 rats with subcutaneous fibrosarcoma tumor allografts were used in all in vivo experiments. Phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine and polyoxyethylene-40 stearate were used to create either oxygen microbubbles (OMBs) with the use of oxygen gas or nitrogen microbubbles (NMBs) with nitrogen gas. The OMBs or NMB’s (served as a negative control) are injected intra-tumorally immediately before the start of radiation delivery. A tumor dose of 15Gy is delivered using 6MV photon beam (2cm x 2cm) on a Siemen Primus accelerator. Tumor volume was measured using ultrasound imaging every 3 days for 31 days.

Results: The OMB injection increased tumoral oxygenation by ~30% while the NMB injection decreased the tumoral oxygenation by ~7%. (n=4 per group). This increase peaks around 90 sec post injection and remains elevated for only 15 min. The RT+OMB group significantly improved tumor control compared to the RT-alone and RT+NMB groups (p<0.05, n=6 per group).

Conclusion: We have demonstrated that OMB injection alone immediately before radiation delivery safely reduced tumor hypoxia and improved tumor control on a rat tumor model.

Funding Support, Disclosures, and Conflict of Interest: This work is partially supported by NIH F31 CA220970 and R21 RHL129144


Hypoxia, Tumor Control, Radiosensitivity


TH- Radiobiology(RBio)/Biology(Bio): Bio- blood flow and vascular

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