99mTc-Annexin A5 for noninvasive characterization of atherosclerotic lesions:: imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
99mTc-Annexin A5 for noninvasive characterization of atherosclerotic lesions:: imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
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DOI：
10.1007/s00259-006-0289-x
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发表时间：
2007-06-01
影响因子：
9.1
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Ishino, Seigo;Kuge, Yuji;Saji, Hideo
细胞凋亡在晚期动脉粥样硬化病变中常见。Tc-99 m-annexin A5（Tc-99 m-annexin V）已被提议作为动脉粥样硬化斑块中细胞凋亡成像的潜在示踪剂。因此，我们确定了有用的Tc-99 m-膜联蛋白A5作为动脉粥样硬化成像示踪剂在兔模型（心肌梗死倾向渡边遗传性高血压兔; WHHLMI兔）自发性atherosclerosis.Methods的WHHLMI和对照兔静脉注射Tc-99 m-膜联蛋白A5。在体内平面成像后，测量主动脉中的放射性。结果WHHLMI组家兔主动脉中Tc-99 m-Annexin A5的蓄积量是对照组的5.6倍。放射自显影显示在WHHLMI兔中不均匀的多灶性Tc-99 m-annexin A5蓄积。Tc-99 m-Annexin A5在动脉粥样硬化病变中的蓄积最高（6.2 +/- 2.5，%IDxBW/mm（2）10（3）），其次是新生内膜（4.9 +/- 1.3）、纤维粥样硬化（4.5 +/- 1.9）和富含胶原的病变（3.3 +/- 1.4）。区域Tc-99 m-annexin A5积累与TUNEL阳性细胞密度、巨噬细胞密度和“脆弱性指数”（形态不稳定特征的指数）显著相关。结论在WHHLMI兔中，IV级动脉粥样硬化斑块中Tc-99 m-annexin A5的蓄积高于其他稳定性病变。Tc-99 m-Annexin A5可用于鉴别动脉粥样硬化破裂风险较高的动脉粥样硬化，并可能用于评估抗动脉粥样硬化治疗的反应。
Apoptosis is commonly observed in advanced atherosclerotic lesions. Tc-99m-annexin A5 (Tc-99m-annexin V) has been proposed as a potential tracer for imaging apoptosis in atherosclerotic plaques. Accordingly, we determined the usefulness of Tc-99m-annexin A5 as an atherosclerosis imaging tracer in a rabbit model (myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits; WHHLMI rabbits) of spontaneous atherosclerosis.Methods The WHHLMI and control rabbits were injected intravenously with Tc-99m-annexin A5. After in vivo planar imaging, the radioactivity in the aorta was measured. Autoradiography, TUNEL staining, Azan-Mallory staining and immunohistological studies were performed serially throughout the aorta.Results Tc-99m-Annexin A5 accumulation in the aorta of the WHHLMI rabbits was 5.6-fold higher than in that of control rabbits. Autoradiography showed heterogeneous multifocal accumulation of Tc-99m-annexin A5 in WHHLMI rabbits. Tc-99m-Annexin A5 accumulation was highest in the atheromatous lesions (6.2 +/- 2.5, %IDxBW/mm(2) 10(3)), followed in decreasing order by neointimal (4.9 +/- 1.3), fibroatheromatous (4.5 +/- 1.9), and collagen-rich lesions (3.3 +/- 1.4). The regional Tc-99m-annexin A5 accumulation was significantly correlated with the TUNEL-positive cell density, macrophage density and "vulnerability index," an index of the morphological destabilized characteristics. The in vivo imaging clearly visualized the atherosclerotic lesions in WHHLMI rabbits.Conclusion The present study in WHHLMI rabbits showed higher Tc-99m-annexin A5 accumulation in grade IV atheroma than in other more stable lesions. Tc-99m-Annexin A5 may be useful in identifying atheroma that is at higher risk for rupture and possibly in assessing the response to anti-atherosclerotic therapy.