Ultrasound-induced cavitation and passive acoustic mapping: SonoTran platform performance and short-term safety in a large-animal model

Abstract

Ultrasound-induced cavitation is currently under investigation for several potential applications in cancer treatment. Among these, the use of low-intensity ultrasound, coupled with the systemic administration of various cavitation nuclei, has been found to enhance the delivery of co-administered therapeutics into solid tumors. Effective pharmacological treatment of solid tumors is often hampered, among various factors, by the limited diffusion of drugs from the bloodstream into the neoplastic mass and through it, and SonoTran holds the potential to tackle this clinical limitation by increasing the amount of drug and its distribution within the ultrasound-targeted tumor tissue. Here we use a clinically ready system (SonoTran Platform) composed of a dedicated ultrasound device (SonoTran System) capable of instigating, detecting and displaying cavitation events in real time by passive acoustic mapping and associated cavitation nuclei (SonoTran Particles), to instigate cavitation in target tissues and illustrate its performance and safety in a large-animal model. This study found that cavitation can be safely triggered and mapped at different tissue depths and in different organs. No adverse effects were associated with infusion of SonoTran Particles, and ultrasound-induced cavitation caused no tissue damage in clinically targetable organs (e.g., liver) for up to 1 h. These data provide evidence of cavitation initiation and monitoring performance of the SonoTran System and the safety of controlled cavitation in a large-animal model using a clinic-ready platform technology.

Keywords: Cavitation; Drug delivery; Passive acoustic mapping; Targeted therapy; Ultrasound.