Enhancing ultrasound-mediated tumor ablation with phase-shift nanoemulsion It is well documented that microbubbles can enhance the absorption of ultrasound in tissue. Thus, it may be possible to improve the efficiency and clinical utility of ultrasound ablation for cancer therapy by introducing or creating microbubbles within the tumor. Unfortunately, the pressure required for creating bubbles in tissue exceeds 100 atmospheres, and the bubbles created collapse violently and damage tissue mechanically before fragmenting into smaller, less responsive gas bodies. In order to reduce the pressure required for bubble formation in vivo, we have developed a liquid perfluorocarbon phase-shift nanoemulsion (PSNE) that can be vaporized in a controlled and predictable manner, forming microbubbles when and where needed. We have shown in previous studies that PSNE can be vaporized with short acoustic pulses, and the threshold for vaporization depends upon the size, composition of the liquid perfluorocarbon core, and ambient temperature. Furthermore, we have shown that PSNE can extravasate through fenestrae in leaky tumor vasculature and populate the tumor interstitium with cavitation nuclei. Upon acoustic vaporization of the PSNE, the bubbles formed are used to enhance tissue absorption of transmitted ultrasound, resulting in the ablation of larger tumor volumes using shorter and less powerful ultrasound exposures. This work will test the use of PSNE to enhance noninvasive focused ultrasound thermal ablation guided by magnetic resonance imaging and thermometry in renal cancer. A combination of in vitro and in vivo studies will be conducted to assess the biodistribution and tumor accumulation of PSNE as function of physicochemical properties, identify vaporization and cavitation thresholds as a function of perfluorocarbon composition, evaluate the spatial correlation between sustained cavitation activity and heat deposition, and assess the response of tumors and animal survival to bubble-enhanced ablation therapy.
Kidney cancer is difficult to eradicate due to limited treatment options. The research outlined in this proposal will develop technology and protocols for localized treatment of solid tumors within the kidney using focused ultrasound with negligible adverse side effects. Ultimately, this technology has the potential to increase patient survival and improve the quality of patient care.
| Crake, Calum; Papademetriou, Iason T; Zhang, Yongzhi et al. (2018) Simultaneous Passive Acoustic Mapping and Magnetic Resonance Thermometry for Monitoring of Cavitation-Enhanced Tumor Ablation in Rabbits Using Focused Ultrasound and Phase-Shift Nanoemulsions. Ultrasound Med Biol 44:2609-2624 |
| Crake, Calum; Meral, F Can; Burgess, Mark T et al. (2017) Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy. Phys Med Biol 62:6144-6163 |
| Papademetriou, Iason T; Porter, Tyrone (2015) Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer. Ther Deliv 6:989-1016 |
| Kopechek, Jonathan A; Park, Eun-Joo; Zhang, Yong-Zhi et al. (2014) Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions. Phys Med Biol 59:3465-81 |
