Commercially Available Ultrasound Contrast Agents: Factors Contributing to Favorable Outcomes With Ultrasound-Mediated Drug Delivery and Ultrasound Localization Microscopy Imaging

Abstract Ultrasound contrast agents (UCAs) are microbubbles comprising an inert gas core stabilized by an encapsulating shell, which serves to increase the signal-to-noise ratio of blood-to-tissue in diagnostic ultrasound imaging. More recently, research has investigated the use of UCAs to combine both diagnostics and therapeutic outcomes in an amalgamated approach, designated ‘theranostics.’ Two examples of theranostic based approaches include the use of super-resolution imaging with ultrasound localized microscopy (ULM) and ultrasound-mediated drug delivery (UMDD). Both ULM and UMDD have been shown to have the potential to improve both patient care and clinical outcomes. Currently, there are 4 commercially available global UCAs licensed for clinical use. The physico-chemical properties of each of these UCAs influence its potential theranostic efficacy. Because of differences in their composition and/or manufacturing processes, each UCA has different characteristics that contribute to different i n vivo resonance behavior, which in turn influences their effective clinical applications. This review highlights the key physico-chemical characteristic differences of the 4 commercially available contrast agents, with specific emphasis on their gaseous core, shell composition, and microbubble volume distribution, while providing novel insights into their benefits for supporting emerging clinical technologies, specifically ULM and UMDD.