Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.
To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1).



The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated.



The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group.



The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.|Department of Ultrasound, North China University of Science and Technology Affiliated Hospital, Tangshan, China.
Fang
F
Xie
Pharmacology Research Department, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Zhi-Ping
ZP
Li
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Hong-Wei
HW
Wang
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Xiang
X
Fei
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Zi-Yu
ZY
Jiao
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Wen-Bo
WB
Tang
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Jie
J
Tang
Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
Yu-Kun
YK
Luo
D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D042241:Early Diagnosis; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles / Q000378:metabolism; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D011817:Rabbits; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000378:metabolism*; D014463:Ultrasonography / Q000379:methods
D003287:Contrast Media; D018799:Intercellular Adhesion Molecule-1