Abstract 14796: Magnetic Targeted Microbubbles Superior to Dual-targeting Microbubbles for Molecular Imaging of Endothelial Inflammation in Large Arteries
Background: Application of site-targeted microbubbles for contrast-enhanced ultrasound (CEU) imaging of endothelial inflammation in large arteries is limited due to the “axial flow” phenomenon and high shear stress, thus resulting in the insufficient binding. Dual-targeting microbubbles may increase microbubble retention to target under high shear stress. However, this strategy does not specifically address the “axial flow”. We, therefore, hypothesized that the novel magnetic microbubbles targeted to P-selectin (MBpM), which can be manipulated by a magnetic field (MF) to flow away from the centerline and slow down, may be superior to dual-targeting to P-selectin microbubbles (MBdual) for molecular imaging of arterial inflammation.
Methods: MBpM and magnetic inactive microbubbles (MBiM) were prepared via a magnetic streptavidin bridge; non-magnetic P-selectin-targeted microbubbles (MBp) and MBdual carried polymeric sialyl LewisX and anti P-selectin antibody were prepared via regular streptavidin. Adherence of the microbubbles to P-selectin was determined in vitro using a flow chamber at 1-24 dyn/cm2 shear stresses with or without MF-guidance. CEU imaging with intravenous injection of those microbubbles, respectively, was performed under MF-guidance in 48 mice, which were treated with injection of TNF-α at dose of 0.5µg around abdominal aorta or with saline control. Video intensity (VI) from the microbubbles targeted to P-selectin was measured. The aortas were harvested for immunohistochemial examination.
Results: The attachment to the P-selectin at high shear stress (16-20dyn/cm2) was noted for MBpM with MF-guidance, and MBdual no matter with or without MF-guidance, while the attachment number of MBpM was 1.9 to 3.0-fold higher than those of MBdual (P<0.01). As expected, the microbubbles targeted to P-selectin on imflamatory endothelium of aortas were clearly shown after MBpM injection with CEU under MF-guidance, but only slightly seen after MBdual. The VI of MBpM was significantly greater than that of MBdual (31.3±5.2 vs 11.4±3.9, P<0.01).
Conclusions: MBpM are superior to MBdual for targeting to the P-selectin under high shear stress, and resulting in a better molecular imaging of P-selectin in large arterial inflammation with CEU.
- © 2011 by American Heart Association, Inc.