Ultrasound and microbubbles: A role in cancer

Successful cancer treatment relies on the sensitivity to monitor cancer response to therapy and the ability to efficiently deliver drugs to the tumor. Cancer research has continuously improved patient outcomes over the last decades; however, it is still the second leading cause of death in the United States. It is essential to improve methods to progress all areas of cancer treatment, including monitoring and drug delivery. Ultrasound (US) is a popular clinical imaging modality due to its low levels of radiation, portability, and cost effective imaging. These advantageous characteristics have allowed for novel research advancements in the US field including drug delivery, molecular US imaging, and molecular targeted delivery. The addition of microbubbles (MBs) has immensely expanded the potential of US in these areas of imaging and drug delivery. MBs are non-toxic, gas-filled contrast agents which mechanically oscillate, enhancing the signal-to-tissue ratio during imaging of the vasculature. MBs also have the ability to stimulate cellular and vascular permeability when exposed to properly applied low-intensity US fields. This transient increase in membrane permeability introduces a window for more effective localized drug uptake in cancerous masses. This effective increase shows potential to improve tumor delivery of anti-cancer agents, such as chemotherapeutics, targeted antibodies (Ab), and adenovirus (Ad). Evaluation of US parameters further facilitate this technology through the avoidance of potential bioeffects, while maintaining a safe, noninvasive, and effective therapeutic strategy. Functionalizing MBs, and creating a targeted molecular US approach, demonstrates potential to more efficiently monitor therapeutic response and enhance drug delivery in cancer. This dissertation describes strategies for improving localized therapeutic delivery in cancer and evaluation of response to treatment using ultrasonic techniques. These techniques are explored in preclinical primary cancer animal models and present significant potential for cancer treatment.

Keywords: cancer, contrast-enhanced ultrasound imaging, microbubbles, molecular ultrasound, ultrasound, ultrasound-stimulated drug delivery