Editors' ChoiceTherapeutic Ultrasound

Bubble, Bubble, Tumor in Trouble

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Science Translational Medicine  08 Feb 2012:
Vol. 4, Issue 120, pp. 120ec23
DOI: 10.1126/scitranslmed.3003795

Cancerous tumors grow larger in part by stimulating angiogenesis—forming new but disorganized blood vessels that supply nutrients to the tumor. These vessels have intrinsic wall defects that are not seen in normal vessels, such as gaps between endothelial cells and the absence of smooth muscle around the endothelial cells and the basement membrane. Liu et al. leveraged these intrinsic differences between tumor neovasculature and normal vessels to target only the tumor-derived vessels while maintaining normal tissue.

Gas-filled microbubbles are similar in size to red blood cells; microbubbles are used as ultrasound contrast agents because they circulate only within the vascular lumen. However, when microbubble contrast agents are subjected to certain types of ultrasound, they can undergo rapid expansion and contraction (cavitation). This cavitation can lead to mechanical damage of the blood vessels and cause weak neovasculature to fall apart; on the other hand, normal blood vessels are more resistant to this damage. Liu et al. now show in rats that this treatment disrupted tumor-specific blood supply routes and led to tumor cell death and necrosis within 24 hours. Normal surrounding tissue initially showed a drop in perfusion; however, there was recovery within an hour, and histology did not show any vascular disruption.

Thus, the microbubbles can selectively target weaker vessel structures with mechanical disruption that stronger, normal vessels can withstand. This new approach may represent a new form of physical anti-angiogenesis therapy. By stopping up the access and passage of blood, microbubbles may shake the tumor's fell purpose.

Z. Liu et al., Disruption of tumor neovasculature by microbubble enhanced ultrasound: A potential new physical therapy of anti-angiogenesis. Ultrasound Med. Biol. 38, 253–261 (2012). [PubMed]

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