von zur Muhlen C, von Elverfeldt D, Moeller J A, Choudhury R P, Paul D, Hagemeyer C E, Olschewski M, Becker A, Neudorfer I, Bassler N, Schwarz M, Bode C, Peter K
Department of Cardiology and Angiology, University of Freiburg, 79106 Freiburg, Germany.
Circulation. 2008 Jul 15;118(3):258-67. doi: 10.1161/CIRCULATIONAHA.107.753657. Epub 2008 Jun 23.
Platelets are the key to thrombus formation and play a role in the development of atherosclerosis. Noninvasive imaging of activated platelets would be of great clinical interest. Here, we evaluate the ability of a magnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIOs) and a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa to image carotid artery thrombi and atherosclerotic plaques.
Anti-LIBS antibody or control antibody was conjugated to 1-microm MPIOs (LIBS MPIO/control MPIO). Nonocclusive mural thrombi were induced in mice with 6% ferric chloride. MRI (at 9.4 T) was performed once before and repeatedly in 12-minute-long sequences after LIBS MPIO/control MPIO injection. After 36 minutes, a significant signal void, corresponding to MPIO accumulation, was observed with LIBS MPIOs but not control MPIOs (P<0.05). After thrombolysis, in LIBS MPIO-injected mice, the signal void subsided, indicating successful thrombolysis. On histology, the MPIO content of the thrombus, as well as thrombus size, correlated significantly with LIBS MPIO-induced signal void (both P<0.01). After ex vivo incubation of symptomatic human carotid plaques, MRI and histology confirmed binding to areas of platelet adhesion/aggregation for LIBS MPIOs but not for control MPIOs.
LIBS MPIOs allow in vivo MRI of activated platelets with excellent contrast properties and monitoring of thrombolytic therapy. Furthermore, activated platelets were detected on the surface of symptomatic human carotid plaques by ex vivo MRI. This approach represents a novel noninvasive technique allowing the detection and quantification of platelet-containing thrombi.
血小板是血栓形成的关键因素，在动脉粥样硬化的发展过程中发挥作用。对活化血小板进行无创成像具有重大临床意义。在此，我们评估了一种磁共振成像（MRI）造影剂的能力，该造影剂由氧化铁微粒（MPIOs）和一种靶向活化糖蛋白IIb/IIIa上配体诱导结合位点（LIBS）的单链抗体组成，用于对颈动脉血栓和动脉粥样硬化斑块进行成像。
将抗LIBS抗体或对照抗体与1微米的MPIOs偶联（LIBS MPIO/对照MPIO）。用6%的氯化铁在小鼠体内诱导形成非闭塞性壁血栓。在注射LIBS MPIO/对照MPIO之前进行一次MRI（9.4 T）检查，并在注射后以12分钟的序列重复进行多次检查。36分钟后，LIBS MPIO组观察到与MPIO聚集相对应的明显信号缺失，而对照MPIO组未观察到（P<0.05）。溶栓后，在注射LIBS MPIO的小鼠中，信号缺失消失，表明溶栓成功。组织学检查显示，血栓中的MPIO含量以及血栓大小与LIBS MPIO诱导的信号缺失显著相关（均P<0.01）。对有症状的人颈动脉斑块进行体外孵育后，MRI和组织学检查证实LIBS MPIO与血小板黏附/聚集区域结合，而对照MPIO则未结合。
LIBS MPIO能够对活化血小板进行具有优异对比特性的体内MRI成像，并监测溶栓治疗。此外，通过体外MRI在有症状的人颈动脉斑块表面检测到了活化血小板。这种方法代表了一种新型的无创技术，可用于检测和定量含血小板血栓。
