Equipe de recherche 'Pharmacologie de la Circulation Cérébrale' EA 4475, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, 75006 Paris, France.
Contrast Media Mol Imaging. 2013 Mar-Apr;8(2):157-64. doi: 10.1002/cmmi.1512.
Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nanoparticular contrast agent P03011, an USPIO (ultrasmall superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or nontargeted USPIO P03007 were injected 5 h after ischemia (100 µmol iron kg⁻¹; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage.
血管损伤在中风后起着关键作用,主要导致水肿、出血和中风复发。因此,用于描述血管病变的工具是一种真正的医疗需求。在这种情况下,专门的纳米级对比剂 P03011 被开发出来,它是一种与靶向 VCAM-1(血管细胞黏附分子-1)的肽结合的 USPIO(超顺磁性氧化铁纳米颗粒),用于检测这种血管炎症反应的主要成分。本研究旨在证明靶向 USPIO P03011 检测中风后小鼠脑缺血时 VCAM-1 的能力。首先,通过免疫组织化学检测我们的脑缺血再灌注模型中 VCAM-1 的表达时间过程。其次,在缺血后 5 小时(100μmol 铁 kg⁻¹;静脉注射)注射 P03011 或非靶向 USPIO P03007,并在缺血后 24 小时进行体内和离体 MRI。然后对脑切片进行双重标记免疫荧光,以检测 USPIO 和 VCAM-1。在我们的模型中,缺血后 24 小时 VCAM-1 的表达显著上调。在接受 P03011 的动物中,在缺血后 24 小时进行的体内和离体 MRI 均显示出低信号焦点,这些焦点可能对应于铁颗粒。组织学分析显示靶向 USPIO 和 VCAM-1 的共定位。这项研究表明,在脑缺血模型中可以使用 USPIO P03011 检测 VCAM-1。这种对比剂可能是一种很有前途的临床工具,可以根据血管损伤来描述缺血性病变。