利用血管细胞黏附分子1单链抗体片段对易损动脉粥样硬化斑块进行单光子发射计算机断层扫描（SPECT）和荧光成像
SPECT and fluorescence imaging of vulnerable atherosclerotic plaque with a vascular cell adhesion molecule 1 single-chain antibody fragment.
作者信息
Liu Chunbao, Zhang Xiao, Song Yiling, Wang Yichun, Zhang Fengzhen, Zhang Yingying, Zhang Yongxue, Lan Xiaoli
机构信息
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
出版信息
Atherosclerosis. 2016 Nov;254:263-270. doi: 10.1016/j.atherosclerosis.2016.09.005. Epub 2016 Sep 13.
BACKGROUND AND AIMS
Early detection and evaluation of vulnerable atherosclerotic plaque are important for risk stratification and timely intervention, and vascular cell adhesion molecule 1 (VCAM1) assists in adhesion and recruitment of inflammatory cells to vulnerable lesions. We labeled a single-chain variable fragment (scFv) of VCAM1 with technetium (Tc) and fluorescent markers to investigate its potential utility in detecting vulnerable plaques in animal models of atherosclerosis.
METHODS
We labeled VCAM1 scFv with Tc and cyanine5 (CY5) and evaluated the probes on apolipoprotein E gene-deficient mice and New Zealand White rabbits with induced atherosclerosis. Histopathology and Western blot examinations confirmed atherosclerotic plaque and VCAM1 expression in the aortas. In vivo biodistribution of Tc-scFv-VCAM1 was studied. Abdominal organs of mice were removed after CY5-scFv-VCAM1 administration for aortic fluorescence imaging. Rabbits SPECT imaging of Tc-scFv-VCAM1 was performed and autoradiography (ARG) of the aortas was checked to confirm the tracer uptake.
RESULTS
The radiochemical purity of Tc-scFv-VCAM1 was 98.72± 1.04% (n = 5) and its specific activity was 7.8 MBq/μg. Biodistribution study indicated predominant probe clearance by kidneys. In fluorescence imaging, stronger signal from CY5-scFv-VCAM1 in the aorta was observed in atherosclerotic mice than that in controls. SPECT imaging with Tc-scFv-VCAM1 showed tracer uptake in the abdominal aorta and the aortic arch of atherosclerotic animals. ARG confirmed tracer uptake in the aortas of atherosclerotic rabbits, with higher uptake ratios of aortic arch/descending aorta in experimental animals (4.45 ± 0.63, n = 5) than controls (1.12 ± 0.15, n = 5; p < 0.05).
CONCLUSIONS
SPECT and fluorescence imaging results showed the feasibility and effectiveness of detecting vulnerable plaque with scFv of VCAM1, indicating its potential for early diagnosis and evaluation of atherosclerosis.
背景与目的
早期检测和评估易损动脉粥样硬化斑块对于风险分层和及时干预至关重要，血管细胞黏附分子1（VCAM1）有助于炎症细胞黏附和募集至易损病变部位。我们用锝（Tc）和荧光标记物标记VCAM1的单链可变片段（scFv），以研究其在动脉粥样硬化动物模型中检测易损斑块的潜在效用。
方法
我们用Tc和菁染料5（CY5）标记VCAM1 scFv，并在载脂蛋白E基因缺陷小鼠和诱导动脉粥样硬化的新西兰白兔上评估这些探针。组织病理学和蛋白质印迹检查证实主动脉中有动脉粥样硬化斑块和VCAM1表达。研究了Tc-scFv-VCAM1在体内的生物分布。给予CY5-scFv-VCAM1后，取出小鼠腹部器官进行主动脉荧光成像。对兔子进行Tc-scFv-VCAM1的单光子发射计算机断层扫描（SPECT）成像，并检查主动脉的放射自显影（ARG）以确认示踪剂摄取情况。
结果
Tc-scFv-VCAM1的放射化学纯度为98.72±1.04%（n = 5），其比活度为7.8 MBq/μg。生物分布研究表明，肾脏是探针清除的主要途径。在荧光成像中，动脉粥样硬化小鼠主动脉中CY5-scFv-VCAM1的信号比对照组更强。用Tc-scFv-VCAM1进行的SPECT成像显示，动脉粥样硬化动物的腹主动脉和主动脉弓有示踪剂摄取。ARG证实动脉粥样硬化兔子的主动脉有示踪剂摄取，实验动物主动脉弓/降主动脉的摄取率（4.45±0.63，n = 5）高于对照组（1.12±0.15，n = 5；p < 0.05）。
结论
SPECT和荧光成像结果表明，用VCAM1的scFv检测易损斑块具有可行性和有效性，表明其在动脉粥样硬化早期诊断和评估方面具有潜力。
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