Molecular imaging of atherosclerotic plaque with lipid nanobubbles as targeted ultrasound contrast agents

Abstract

Molecularly-targeted nanobubbles (NBs) offer opportunities to improve the ability of ultrasound imaging to identify specific pathological tissue from healthy tissue. In this work, we aimed to design ligands-conjugated, nanosized, lipid ultrasound contrast agents (UCAs) and apply the agents in the ultrasound imaging of atherosclerotic plaque. Anti-VEGFR-2 ligands were conjugated to UCAs using the noncovalent biotin-avidin linker method. Several investigations were used to determine the morphology and performance of the targeted UCAs, including surface morphology, size distribution and ligands conjunction efficiency. The prepared targeted UCAs were utilized in vivo ultrasound imaging to detect rabbit abdominal aorta atherosclerotic plaque and to investigate the acoustic behavior in a rabbit kidney model. The results implied that the nanosized UCAs carrying anti-VEGFR-2 ligands would facilitate site-specific recognition of atherosclerosis and can provide unique advantages in targeted ultrasound molecular imaging.

Keywords: Atherosclerotic plaque; Molecular imaging; Nanobubbles; Targeted ligands; Ultrasound contrast agents.