title: Ultrasound molecular imaging of arterial thrombi with novel microbubbles modified by cyclic RGD in vitro and in vivo.
abstract: Despite immense potential, ultrasound molecular imaging (UMI) of arterial thrombi remains very challenging because the high-shear arterial flow limits binding of site-targeted microbubbles to the thrombi. The linear Arg-Gly-Asp (RGD) peptides have been successfully applied to evaluate venous, atrial, and arteriolar thrombi, but have thus far failed in the detection of arterial thrombi. Cyclic RGD (Arg-Gly-Asp-D-Phe-Cys) is a cyclic conformation of linear RGD peptides, which has much higher binding-affinity and selectivity for binding to the glycoprotein (GP) IIb/IIIa receptor than its linear counterpart and thus is likely to be an optimal targeted molecular probe for ultrasound molecular imaging of arterial thrombi. In this study, we sought to assess the feasibility of a novel microbubble conjugated with cyclic RGD (Mb-cyclic RGD) in UMI of arterial thrombi  in vitro  and  in vivo . As expected, Mb-cyclic RGD had greater GP IIb/IIIa-targeted binding capability in all shear stress conditions. In addition, the shear stress at half-maximal detachment of Mb-cyclic RGD was 5.7-fold higher than that of microbubbles with non-specific peptide (Mb-CON) (p<0.05). Mb-cyclic RGD enhanced the echogenicity of the platelet-rich thrombus  in vitro  whereas Mb-CON did not produce enhancement. In the  in vivo  setting, optimal signal enhancement of the abdominal aortic thrombus was displayed with Mb-cyclic RGD in all cases. Mean video intensity of the abdominal aortic thrombi with Mb-cyclic RGD was 3.2-fold higher than that with Mb-CON (p<0.05). The novel Mb-cyclic RGD facilitated excellent visualisation of arterial thrombi using UMI and showed great promise for clinical applications.
authors: Department of Cardiology, Nanfang Hospital, Southern Medical University, #1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors: Guangquan
authors: G
authors: Hu
authors: Cheng
authors: C
authors: Liu
authors: Yulin
authors: Y
authors: Liao
authors: Lic
authors: L
authors: Yang
authors: Ruizhu
authors: R
authors: Huang
authors: Juefei
authors: J
authors: Wu
authors: Jiajia
authors: J
authors: Xie
authors: Kaviraj
authors: K
authors: Bundhoo
authors: Ying
authors: Y
authors: Liu
authors: Jianping
authors: J
authors: Bin
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D045423:Microbubbles; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D033081:Shear Strength; D013314:Stress, Mechanical; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014465:Ultrasonics
chemical_list: D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid