Ultrasound Molecular Imaging of Atherosclerosis for Early Diagnosis and Therapeutic Evaluation through Leucocyte-like Multiple Targeted Microbubbles

Our study provides a promising ultrasound molecular imaging probe for early-stage diagnosis and therapeutic evaluation of atherosclerosis.

By mimicking the leucocytes that are recruited to the vessel wall during the initiation of atherosclerosis through selectin-dependent arrest and cell adhesion molecule-mediated firm cell adhesion, we developed VCAM-1/ICAM-1/P-selectin-targeted MBVIS by integrating VCAM-1 and ICAM-1 antibodies and synthetic polymeric sialyl Lewis X (sLex) onto the MB surface.

The resulting MBVIS had a high affinity to inflammatory bEnd.3 cells in both static and dynamic flow conditions. Significantly enhanced ultrasound imaging signals were achieved by MBVIS in detecting the atherosclerosis progress when compared with the single- or dual-targeted MBs. Taking advantage of the artificial MBVIS, less ultrasound imaging signals were found in the atorvastatin-treated, but not placebo-treated, ApoE-deficient mice with atherosclerosis, revealing a potential therapeutic efficacy of atorvastatin for early stage atherosclerosis. This was further confirmed by histologic staining examination. Conclusions: Our study provides a promising ultrasound molecular imaging probe for early-stage diagnosis and therapeutic evaluation of atherosclerosis.