Sensitization of hypoxic tumors to radiation therapy using ultrasound sensitive oxygen microbubbles
Menée à l'aide d'un modèle murin, cette étude met en évidence l'intérêt de microbulles d'oxygène sensibles aux ultrasons pour améliorer la réponse des tumeurs hypoxiques aux rayonnements ionisants
Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment which has been shown to result in both chemo- and radiotherapy resistance. Systemic delivery of oxygen prior to therapy has proven largely ineffective in reversing this resistance. Surfactant-shelled oxygen microbubbles that can be injected intravenously and used to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound have been previously reported. In this work, we show that these agents successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline or untriggered oxygen microbubbles (p < 0.001). 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 < 0.03). Findings from this study demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.