Molecular imaging of atherosclerotic plaques targeted to oxidized LDL receptor LOX-1 by SPECT/CT and magnetic resonance.
Molecular imaging of atherosclerotic plaques targeted to oxidized LDL receptor LOX-1 by SPECT/CT and magnetic resonance.
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DOI：
10.1161/circimaging.109.896654
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
Meyer CH
中科院分区：
文献类型：
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作者：
Li D;Patel AR;Klibanov AL;Kramer CM;Ruiz M;Kang BY;Mehta JL;Beller GA;Glover DK;Meyer CH
氧化LDL受体LOX-1在动脉粥样硬化中起着至关重要的作用。我们试图检测和评估动脉粥样硬化斑块在体内使用SPECT/CT和磁共振成像（MRI）使用的分子探针靶向LOX-1。使用西方饮食的Apo E−/−小鼠和致动脉粥样硬化饮食的LDLR−/−和LDLR −/−/LOX-1−/−小鼠。成像探针由修饰有LOX-1抗体（LOX-1）或非特异性IgG（nIgG）、111 In或钆（Gd）和DiI荧光标记物的脂质体组成。在静脉内注射（150 μl）用111 In（600 μCi）或Gd（0.075 mmol/kg）标记的LOX-1（或nIgG）探针后24小时进行体内成像，随后切除主动脉用于磷光体成像和苏丹IV染色或荧光成像和H&E染色。LOX-1探针也与特定的细胞类型，细胞凋亡和MMP 9表达使用冷冻主动脉切片共定位。LOX-1探针的SPECT/CT成像显示Apo E−/−小鼠（n=8）的主动脉弓热点，并通过荧光成像证实。MRI显示，在使用LOX-1（n=7）而非nIgG探针（n=5）的LDLR−/−小鼠中，动脉粥样硬化斑块中Gd显著增强。在注射LOX-1探针的LDLR−/−/LOX-1−/−小鼠中未观察到信号增强（n=5）。这些结果通过离体荧光成像证实。LOX-1探针优先结合到斑块肩部，该区域具有易损斑块特征，包括广泛的LOX-1表达、巨噬细胞积聚、凋亡和MMP 9表达。LOX-1可作为动脉粥样硬化斑块分子成像的靶点。此外，LOX-1成像可以识别易破裂的动脉粥样硬化斑块。
The oxidized-LDL receptor LOX-1 plays a crucial role in atherosclerosis. We sought to detect and assess atherosclerotic plaque in vivo using SPECT/CT and magnetic resonance imaging (MRI) using a molecular probe targeted at LOX-1. Apo E−/− mice on Western diet and LDLR−/− and LDLR−/−/LOX-1−/− mice on atherogenic diet were used. Imaging probes consisted of liposomes decorated with LOX-1 antibodies (LOX-1) or nonspecific IgG (nIgG), 111In or gadolinium (Gd), and DiI fluorescence markers. In vivo imaging was performed 24 hrs after intravenous injection (150 µl) of LOX-1 (or nIgG) probes labeled with either 111In (600 µCi) or Gd (0.075 mmol/kg) followed by aortic excision for phosphor imaging and Sudan IV staining or fluorescence imaging and H&E staining. The LOX-1 probe was also co-localized with specific cell types, apoptosis, and MMP9 expression using frozen aortic sections. SPECT/CT imaging of the LOX-1 probe showed aortic arch hotspots in Apo E−/− mice (n=8), confirmed by phosphor imaging. MRI showed significant Gd enhancement in atherosclerotic plaques in LDLR−/− mice with the LOX-1 (n=7), but not nIgG, probe (n=5). No signal enhancement was observed in LDLR−/−/LOX-1−/− mice injected with LOX-1 probe (n=5). These results were confirmed by ex-vivo fluorescence imaging. The LOX-1 probe bound preferentially to the plaque shoulder, a region with vulnerable plaque features including extensive LOX-1 expression, macrophage accumulation, apoptosis and MMP9 expression. LOX-1 can be used as a target for molecular imaging of atherosclerotic plaque in vivo. Furthermore, LOX-1 imaging may identify rupture-prone atherosclerotic plaque.