Abstract 3559: Dual-Targeted Contrast Enhanced Ultrasound Imaging of Atherosclerosis in Apolipoprotein E gene Knockout Mice
Background. Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall. This study was undertaken to test whether lipid-shelled microbubbles (MB) conjugated to dual ligands, polymeric sialyl LewisX (psLex) and anti-mouse VCAM-1 monoclonal antibody, adhere to athero-sclerotic arteries and produce detectable contrast enhanced images.
Methods. Animal studies were performed in apoE-/- mice (7 male, 3 female) and C57BL/6 controls. apoE-/- mice were fed high-fat western diet for 16–18 weeks and were imaged at 28–32 weeks. Biotinylated psLex and anti-mouse VCAM-1 were coupled to biotinylated MB via streptavidin. 108 MBs were injected via the right jugular vein. Echo studies were performed with an Acuson Sequoia (8.0 MHZ, 15L8 transducer, Contrast Pulse Sequence).The transducer was placed on the right side of the neck. Targeted contrast images were acquired 10 and 15 min after MB injection under low mechanical index, followed by high-MI for 1 min to destroy MBs, and by final background image. Mean pixel video intensity (VI) was obtained by ImageJ. Post mortem dissection microscopic images of arteries images acquired using a digital camera and picture frame software.
Results. VI of targeted MB in apoE-/- mice was significantly higher than in control mice (p<0.01). Specific contrast signal was observed in the aortic arch, innominate artery, subclavian and carotid artery. Post mortem aortic whole mounts of aortic arches showed good correspondence between lesion areas and contrast agent accumulation.
Conclusion: Dual-targeted MBs (psLeX and anti-VCAM-1) attached effectively to atherosclerotic lesions in apoE-/- mice and provided specific contrast images.