Ultrasound molecular imaging of endothelial vascular endothelial growth factor recptor-2 expression during hind-limb ischemia-mediated angiogensis

Abstract

Objective To explore the feasibility of evaluation of mice hind limb ischemia-mediated angiogenesis with ultrasound molecular imaging using molecular probes targeted to angiogenesis endothelial marker VEGFR-2.Methods A mice model of unilateral hind-limb ischemia was induced by femoral artery excision in 12 experimental mice.Ultrasound molecular imaging of the ischemia and contralateral non-ischemia hind-limbs was performed in all mice on day 7 after surgery at 8 minutes after intravenous injection of either VEGFR-2 targeting microbubbles or isotype control microbubbles in random with 30 min interval,and the video intensity (VI) was measured.Following ultrasound imaging,the hind-limb was harvested for immunohistochemical analysis.Results As expected,VI in the ischemia hind-limb was significantly higher (P ＜0.05) for MBvEGFR-2 [(25.6 ± 4.3)U] as compared with MBIso[(6.7 ± 1.6)U].However,the ultrasound signal in the non-ischemia hind-limb was low for both MBvEGFR-2 [4.4 ± 1.5)U] and MBIso [(4.6 ± 1.6)U].A marked endothelial VEGFR-2 expression in ischemia hind-limb was confirmed by immunohistochemistry.Conclusions Ultrasound molecular imaging using molecular probes targeted to angiogenesis endothelial VEGFR-2 can effectively evaluate ischemia-mediated angiogenesis. Key words: Ultrasonography; Molecular imaging ; Ischemia ; Neovascularization, physiologic ; Vascular endothelial growth factor receptor-2