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



MBs were modified with P-selectin antibody (MBPM) or isotype control antibody (MBCM) via a magnetic streptavidin bridge, and MBs were conjugated to P-selectin antibody (MBP) or both P-selectin antibody and PAA-sialyl Lewisx(MBD) via regular streptavidin linker. Adherence of MBs was determined by using a parallel plate flow chamber at variable shear stress (0.5-24 dyn/cm2). Adhesive and magnetic behaviors of MBs were analyzed at 4.0 dyn/cm2or 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.



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



MBPM may be a better molecular probe than MBDfor 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.
Department of Cardiology, Panyu Central Hospital, Guangzhou, China.|StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Weilan
W
Wu
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Xuguang
X
Feng
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Ye
Y
Yuan
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.|Department of Cardiology, Guangzhou Eight People's Hospital, Guangzhou, China.
Ying
Y
Liu
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.|Department of Cardiology, Guangzhou Eight People's Hospital, Guangzhou, China.
Meiyu
M
Li
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Jianguo
J
Bin
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Yunbin
Y
Xiao
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wangjun
W
Liao
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Yulin
Y
Liao
Department of Cardiology, Panyu Central Hospital, Guangzhou, China. 18922238031@189.cn.
Wenzhu
W
Zhang
StateKey Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China. jianpingbin@126.com.
Jianping
J
Bin
D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging* / Q000473:pathology*; D002448:Cell Adhesion; D003287:Contrast Media / Q000737:chemistry; D042783:Endothelial Cells / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D008280:Magnetics / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D019007:P-Selectin / Q000378:metabolism*; D014463:Ultrasonography
D003287:Contrast Media; D019007:P-Selectin
Inflammation; Microbubbles; P-selectin; Ultrasound molecular imaging
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