Ultrasound Nano-scale Phase-Change Contrast Agents for Tumor Radiosensitization
Wednesday, February 8, 2023
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
Ultrasound Nano-scale Phase-Change Contrast Agents for Tumor Radiosensitization
Speaker:
Hebah Falatah, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisors:
John R. Eisenbrey, PhD
Associate Professor
Department of Radiology
Thomas Jefferson University
Margaret A. Wheatley, PhD
John M. Reid Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
Primary liver cancer is the third cause of cancer death worldwide, with 906,000 new cases and 830,000 deaths. Of these, 75-85% of patients are hepatocellular carcinoma (HCC), while the remaining 15-25% are intrahepatic cholangiocarcinoma and other types. Due to the late clinical presentation of the disease and treatment limitations of chemotherapy and immunotherapies, HCC has a poor prognosis. Localized radiotherapy in the early and mid-stages of HCC has shown some success. In such therapy, the hepatic artery supplying blood to the cancer is injected with radioisotope yttrium-90 (Y90), a beta particle emitter that provides localized radiation therapy. Another therapeutic option is external beam radiation (XRT) with MRI or CT guidance. XRT has been used cautiously in HCC treatment due to the radiosensitivity of liver tissue and technological limitations. Fractionated approaches are used to overcome the toxicity to the liver or radiation-induced liver diseases caused by high doses of radiation. The result of these limitations is that the overall five years survival for HCC patients in the United States is 20%, and the two years survival is less than 50%. Therefore, developing more effective HCC treatments is essential to improve patient outcomes.
In recent years, researchers have been exploring a variety of radiosensitizers as a means of overcoming radiotherapy resistance. One promising radiotherapy enhancement mechanism is through the use of ultrasound-mediated microbubble destruction, which has been shown to sensitize solid tumors to radiotherapy through endothelial cell disruption in tumors. Ultrasound microbubbles have a diameter between 1 to 8 μm and consist of a high molecular weight gas encapsulated by a lipid, protein, or polymer shell. However, due to the relatively large size of bubbles, which prevents them from passing into extravascular spaces, researchers developed phase-change contrast agents (PCCAs).
PCCAs can transition from the liquid to the gaseous state under external stimuli. This technology has been widely used in ultrasound medical imaging, vascular occlusion, and cavitation activity enhancement. The small diameters (< 400 nm) of these PCCAs allow them to diffuse and accumulate in solid tumors via the enhanced permeability and retention effect before the phase transition. Using ultrasound as an acoustic stimulus can provide local vaporization as well as cavitation of the resultant microbubble, thereby generating local force in tumor tissues.
This project aims to develop and characterize nano-scale phase change droplets < 200 nm from commercial ultrasound contrast agents and demonstrate their ability to enhance HCC tumor radiosensitization.
Contact Information
Natalia Broz
njb33@drexel.edu