Experimental study on molecular imaging of atherosclerotic plaques by targeted interleukin-18 ultrasonic microbubbles

Abstract

Objective To investigate whether targeted interleukin-18 (IL-18) ultrasonic microbubbles can improve molecular imaging of atherosclerotic plaques. Methods An atherosclerotic plaque rabbit model was established using a high-fat diet and immunologic injury method. The locations of atherosclerotic plaques were verified by ultrasonography. Targeted IL-18 ultrasonic microbubbles were prepared by the biotin-avidin method. After being anesthetized, the experimental rabbits were randomized to use control microbubbles (MBc) and targeted microbubbles (MBt) to perform contrast-enhanced ultrasound examination of atherosclerotic plaques. After rabbits were sacrificed, the targeted plaques were taken for pathological examination and Western-blotting analysis. Results The atherosclerosis model was successfully constructed in 10 experimental rabbits. Light microscope showed stable physical properties of MBt and fluorescence microscopy showed uniform green halos on the surface of MBt. Semiquantitative analysis of contrast-enhanced intensity of targeted plaques revealed that the average intensity of MBc group was 202 ± 18, and that of MBt group was 237 ± 7. The difference was statistically significant (t=6.472, P < 0.001). Pathological examination indicated atheromatous plaques in the lumen of arteries; Western-blotting analysis indicated IL-18 expressions in the plaques. Correlation analysis showed contrast-enhanced intensity of MBc group and IL-18 expression in the plaques had no correlation (r=0.534, P=0.112), while that of MBt group and IL-18 expression had linear positive correlation (r=0.904, P < 0.001). Conclusion MBt can better facilitate the detection of atherosclerotic plaques than MBc and be used for early, sensitive and specific diagnosis and treatment of atherosclerotic plaques. Key words: Interleukin-18; Ultrasound; Targeted microbubble; Atherosclerotic plaques; Molecular imaging