Comparison of Magnetic Microbubbles and Dual-modified Microbubbles Targeted to P-selectin for Imaging of Acute Endothelial Inflammation in the Abdominal Aorta.

PURPOSE

Ultrasound molecular imaging (UMI) has potential to evaluate an inflammatory profile of endothelium. However, it is less successful in large arteries. This study compared magnetic microbubbles (MBs) selectively targeted to endothelial P-selectin and dual-targeting MBs in vitro and in vivo.

PROCEDURES

MBs were modified with P-selectin antibody (MBM) or isotype control antibody (MBM) via a magnetic streptavidin bridge, and MBs were conjugated to P-selectin antibody (MB) or both P-selectin antibody and PAA-sialyl Lewis (MB) via regular streptavidin linker. Adherence of MBs was determined by using a parallel plate flow chamber at variable shear stress (0.5-24 dyn/cm). Adhesive and magnetic behaviors of MBs were analyzed at 4.0 dyn/cm or at a flow rate of 50 mm/s. Attachment of MBs to P-selectin was determined with contrast-enhanced ultrasound (CEU) imaging of murine abdominal aorta inflammation. The expression of P-selectin was assessed by immunohistochemistry.

RESULTS

The adhesive efficacy of MB was greater than MB and MBM, but lower than MBM under all shear stress conditions (P < 0.05). The behaviors of fast-binding and rolling slow down were noted in MB and MBM; meanwhile, magnetic shifting of MBs centerline was presented in MBM. Contrast video intensity (VI) from adhered MBM to P-selectin of the inflammatory aorta was significantly higher than those from MB and MB (P < 0.05).

CONCLUSIONS

MBM may be a better molecular probe than MB for detection of P-selectin on aorta with CEU, likely due to the shifting of axial distribution. Thus, it may improve the detection of the inflammatory profile on large arteries by UMI.