Perfluorocarbon Nanodroplets for Extravascular Imaging Applications
Yarmoska, Steven Karl
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Gas microbubbles are the contrast agent of choice for ultrasound imaging. These agents are excellent for highlighting vasculature; however, their micrometer-scale size prevents them from efficient trafficking within extravascular spaces. Perfluorocarbon nanodroplets (PFCnDs) are a phase-change class of ultrasound contrast agent that were designed to address this challenge. PFCnDs are stable at submicrometer sizes, retaining favorable transport characteristics prior to becoming microbubbles in situ in response to user-initiated activation. These dissertation studies utilized optically triggered perfluorohexane nanodroplets (PFHnDs) for longitudinal extravascular contrast-enhanced ultrasound imaging in the context of metastatic breast cancer. In Aim 1, we optimized the synthesis of and imaging sequence for PFHnDs in order to improve their transport and detection, respectively, within extravascular spaces. In Aim 2, we imaged PFHnDs trafficking through tumor-draining and naïve murine lymphatics and, in parallel, developed a new class of adjuvant-carrying PFHnDs for use as an image-guided therapeutic vehicle in tumor-draining lymphatics. In Aim 3, we attempted to demonstrate PFCnD extravasation from neovasculature into the primary tumor stroma in immunocompetent murine models of breast cancer. Altogether, these studies represent a novel contribution to the field of contrast-enhanced ultrasound research, as they develop and explore new avenues of extravascular applications for PFCnDs. Our findings have the potential to inspire new lines of investigation with PFCnDs and to push the envelope with regards to applications-based phase-change contrast agent research.