A Comparison of [99mTc]Duramycin and [99mTc]Annexin V in SPECT/CT Imaging Atherosclerotic Plaques
A Comparison of [99mTc]Duramycin and [99mTc]Annexin V in SPECT/CT Imaging Atherosclerotic Plaques
复制标题
[99mTc]耐久霉素和[99mTc]Annexin V 在 SPECT/CT 动脉粥样硬化斑块成像中的比较
DOI：
10.1007/s11307-017-1111-9
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发表时间：
2018-04-01
影响因子：
3.1
通讯作者：
Shi, Hongcheng
中科院分区：
文献类型：
--
作者：
Hu, Yan;Liu, Guobing;Shi, Hongcheng
细胞凋亡是不稳定斑块形成的关键因素。本研究旨在评估用放射性标记的短杆菌肽和膜联蛋白V对动脉粥样硬化斑块进行可视化的效用。给载脂蛋白E基因敲除（ApoE(-/-) ）小鼠喂食高脂饮食以诱发动脉粥样硬化，以C57小鼠作为对照。通过常规偶联方案，获得了高纯度的[锝-99m]短杆菌肽和[锝-99m]膜联蛋白V，并将其用于细胞凋亡的体外细胞试验以及动物模型中动脉粥样硬化斑块的体内成像。采用油红O染色、TUNEL染色、苏木精 - 伊红（HE）染色以及CD68免疫染色来评估病变部位脂质沉积情况以及凋亡巨噬细胞的存在，病变部位的局部强度与两种示踪剂的摄取呈正相关。使用了具有高放射化学纯度（分别为97.13 ± 1.52%和94.94 ± 0.65%）且在室温下稳定性良好的[锝-99m]短杆菌肽和[锝-99m]膜联蛋白V。凋亡细胞与[锝-99m]短杆菌肽的结合活性（解离常数Kd为6.92 nM，最大结合量Bmax为56.04 mol/10¹⁹个细胞）显著高于与[锝-99m]膜联蛋白V的结合活性（Kd为12.63 nM，Bmax为31.55 mol/10¹⁹个细胞）。与[锝-99m]膜联蛋白V相比，[锝-99m]短杆菌肽与动脉粥样硬化病变部位的结合更为紧密，斑块与背景的比值更高（20周时，斑块与背景比值P/B分别为8.23 ± 0.91和5.45 ± 0.48；30周时，分别为15.02 ± 0.23和12.14 ± 0.22）。C57对照小鼠中未发现斑块。此外，油红O染色显示，ApoE(-/-) 小鼠在20周和30周时脂质沉积区域显著增加，TUNEL染色和CD68染色证实两种示踪剂的局部摄取部位含有大量凋亡巨噬细胞。因此，这种稳定、清除迅速且特异性高的[锝-99m]短杆菌肽可用于易损动脉粥样硬化斑块的定量分析。
Apoptosis is a key factor in unstable plaques. The aim of this study is to evaluate the utility of visualizing atherosclerotic plaques with radiolabeled duramycin and Annexin V.ApoE(-/-) mice were fed with a high-fat diet to develop atherosclerosis, C57 mice as a control. Using a routine conjugation protocol, highly pure [Tc-99m]duramycin and [Tc-99m]Annexin V were obtained, which were applied for in vitro cell assays of apoptosis and in vivo imaging of atherosclerotic plaques in the animal model. Oil Red O staining, TUNEL, hematoxylin-eosin (HE), and CD68 immunostaining were used to evaluate the deposition of lipids and presence of apoptotic macrophages in the lesions where focal intensity positively correlated with the uptake of both tracers.[Tc-99m]duramycin and [Tc-99m]Annexin V with a high radiochemical purity (97.13 +/- 1.52 and 94.94 +/- 0.65 %, respectively) and a well stability at room temperature were used. Apoptotic cells binding activity to [Tc-99m]duramycin (Kd, 6.92 nM and Bmax, 56.04 mol/10(19) cells) was significantly greater than [Tc-99m]Annexin V (Kd, 12.63 nM and Bmax, 31.55 mol/10(19) cells). Compared with [Tc-99m]Annexin V, [Tc-99m]duramycin bound avidly to atherosclerotic lesions with a higher plaque-to-background ratio (P/B was 8.23 +/- 0.91 and 5.45 +/- 0.48 at 20 weeks, 15.02 +/- 0.23 and 12.14 +/- 0.22 at 30 weeks). No plaques were found in C57 control mice. Furthermore, Oil Red O staining showed lipid deposition areas were significantly increased in ApoE(-/-) mice at 20 and 30 weeks, and TUNEL and CD68 staining confirmed that the focal uptake of both tracers contained abundant apoptotic macrophages.This stable, fast clearing, and highly specific [Tc-99m]duramycin, therefore, can be useful for the quantification of vulnerable atherosclerotic plaques.