Detection of Vulnerable Atherosclerosis Plaques with a Dual-Modal Single-Photon-Emission Computed Tomography/Magnetic Resonance Imaging Probe Targeting Apoptotic Macrophages
Detection of Vulnerable Atherosclerosis Plaques with a Dual-Modal Single-Photon-Emission Computed Tomography/Magnetic Resonance Imaging Probe Targeting Apoptotic Macrophages
复制标题
使用针对凋亡巨噬细胞的双模态单光子发射计算机断层扫描/磁共振成像探针检测易损动脉粥样硬化斑块
DOI：
10.1021/am508118x
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发表时间：
2015-02-04
影响因子：
9.5
通讯作者：
Shi, Hongcheng
中科院分区：
文献类型：
--
作者：
Cheng, Dengfeng;Li, Xiao;Shi, Hongcheng
动脉粥样硬化（AS），特别是易损斑块破裂引起的急性阻塞性血管疾病，是导致死亡的主要原因。因此，需要一种有效的方法来准确预测AS的进展和斑块易损性。本文报道了一种利用单光子发射计算机断层扫描(SPECT)/磁共振成像（MRI）多模态探针构建混合纳米粒子系统的方法，旨在通过实现高灵敏度和高分辨率来全面评估AS进展。超顺磁氧化铁（USPIO）被胺化聚乙二醇（PEG）和羧化聚乙二醇同时覆盖，然后用二乙烯三胺五乙酸功能化Tc-99m，随后用Annexin V靶向易损斑块中丰富的凋亡巨噬细胞。SPECT和MRI所反映的体内显像探针的聚集对病灶的显影一致、准确。SPECT检测到的强放射性信号有助于病灶识别和量化，而基于uspio的t -2加权MRI改善了AS斑块的病灶定位和体积测定。对于随后的离体平面图像，通过免疫组织化学进一步证实靶向作用，包括CD-68和TUNEL染色；同时，证明了浓度程度与Oil Red O染色结果具有统计学相关性。综上所述，这些结果表明，Annexin v修饰的杂交纳米颗粒系统特异性靶向含有凋亡巨噬细胞的易损AS斑块，在有创准确检测易损斑块方面具有重要价值。
Atherosclerosis (AS), especially the vulnerable AS plaque rupture-induced acute obstructive vascular disease, is a leading cause of death. Accordingly, there is a need for an effective method to draw accurate predictions about AS progression and plaque vulnerability. Herein we report on an approach to constructing a hybrid nanoparticle system using a single-photon-emission computed tomography (SPECT)/magnetic resonance imaging (MRI) multimodal probe, aiming for a comprehensive evaluation of AS progression by achieving high sensitivity along with high resolution. Ultrasmall superparamagnetic iron oxide (USPIO) was covered by aminated poly(ethylene glycol) (PEG) and carboxylated PEG simultaneously and then functionalized with diethylenetriaminepentacetate acid for Tc-99m coordination and subsequently Annexin V for targeting apoptotic macrophages abundant in vulnerable plaques. The in vivo accumulations of imaging probe reflected by SPECT and MRI were consistent and accurate in highlighting lesions. Intense radioactive signals detected by SPECT facilitated focus recognization and quantification, while USPIO-based T-2-weighted MRI improved the focal localization and volumetry of AS plaques. For subsequent ex vivo planar images, targeting effects were further confirmed by immunohistochemistry, including CD-68 and TUNEL staining; meanwhile, the degree of concentration was proven to be statistically correlated with the Oil Red O staining results. In conclusion, these results indicated that the Annexin V-modified hybrid nanoparticle system specifically targeted the vulnerable AS plaques containing apoptotic macrophages and could be of great value in the invasively accurate detection of vulnerable plaques.