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PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury

机译:鞘氨氨酸-1-磷酸盐受体1表达对颈动脉损伤大鼠模型血管炎症的宠物研究

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Sphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [11C]TZ3321, a potent S1PR1 radioligand, for imaging vascular inflammation in a rat model of carotid injury. The right common carotid artery of male adult Sprague-Dawley rats was injured by balloon overinflation that denuded the endothelium and distended the vessel wall. Animals received a 60-minute micro-positron emission tomography (micro PET) scan with [11C]TZ3321 at 72 hours after injury. Ex vivo autoradiography was also conducted. The expression and cellular location of S1PR1 were examined by immunohistological analysis. Three-dimensional (3D) reconstruction of the first 100-second microPET/computed tomography (CT) image indicated the location of bilateral common carotid arteries. [11C]TZ3321 displayed significantly higher accumulation (standardized uptake values: 0.93 ± 0.07 vs 0.78 ± 0.09, n = 6, P = .001) in the injured carotid artery than in the contralateral side. Increased tracer uptake in the injured artery was confirmed by autoradiography (photostimulated luminescence measures: 85.5 ± 0.93 vs 71.48 ± 6.22, n = 2). Concordantly, high S1PR1expression was observed in infiltrated inflammatory cells in the injured artery. Our studies demonstrate [11C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expression in inflamed carotid artery. Therefore, [11C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation.
机译:鞘氨酸-1-磷酸盐受体(S1PR)活化在血管炎症反应中起着关键作用。这里,我们报告了[11C] TZ3321的体内验证,有效的S1PR1放射性配体,用于在颈动脉损伤的大鼠模型中成像血管炎症。雄性成人Sprague-Dawley大鼠的正确常见的颈动脉被气球过度损伤,剥落内皮和扩散血管壁。动物在损伤后72小时接受了60分钟的微正电子发射断层扫描(微宠物)扫描[11C] TZ3321。还进行了exVivo放射自显影。通过免疫组织学分析检查S1PR1的表达和细胞位置。第一100秒微移植/计算断层扫描(CT)图像的三维(3D)重建表示双侧常见颈动脉的位置。 TZ3321在受伤的颈动脉中显示出显着较高的积累(标准化摄取值:0.93±0.07,N = 6,P = .001)。通过放射造影确认受伤动脉中的示踪剂增加(光刺激发光措施:85.5±0.93 Vs 71.48±6.22,n = 2)。在受伤动脉中的渗透炎性细胞中观察到高S1pr1表达。我们的研究证明了TZ3321 Micropet能够检测到发炎的颈动脉中S1PR1表达的急性上调。因此,[11C] TZ3321具有宠物放射反射器,用于检测早期炎症反应和监测血管炎症的治疗疗效。

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