| 罗全勇,张志勇,王芳,张毅,陆汉魁,孙树汉,朱瑞森.99mTc-AnnexinB1的制备及其探测细胞凋亡的实验研究[J].中国医学影像技术,2008,24(8):1177~1181 |
| 99mTc-AnnexinB1的制备及其探测细胞凋亡的实验研究 |
| Preparation and bioevaluation of 99mTc-Annexin B1 as a novel radiotracer for apoptosis imaging |
| 投稿时间：2008-03-11 修订日期：2008-05-28 |
| DOI： |
| 中文关键词: 细胞凋亡 膜联蛋白B1 生物分布 放射性核素显像 |
| 英文关键词:Apoptosis Annexin B1 Biodistribution Radioisotope scintigraphy |
| 基金项目:国家自然科学基金(30600155)和上海市青年科技启明星计划(06QA14040)。 |
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| 中文摘要: |
| 目的 制备99mTc-Annexin B1并对其体外、体内生物分布以及探测体内细胞凋亡的潜力进行评价。方法 应用99mTc直接标记蛋白质的方法制备99mTc-Annexin B1。采用与活化人血小板结合实验检测99mTc-Annexin B1的体外生物活性。在正常小鼠体内进行生物分布研究。采用地塞米松诱导小鼠胸腺凋亡的动物模型和anti-Fas单抗诱导小鼠肝脏凋亡的动物模型检测99mTc-Annexin B1探测体内细胞凋亡的潜力,并用TUNEL染色证实细胞凋亡。 结果 直接标记法制备的99mTc-Annexin B1具有很高的放射化学纯度和很好体外稳定性。与活化人血小板的结合实验表明, 99mTc-Annexin B1具有与PS结合的体外生物活性。99mTc-Annexin B1在体内具有较快的清除特性,主要聚集于肾脏。地塞米松诱导18 h后,小鼠胸腺对99mTc-Annexin B1的摄取显著高于对照小鼠胸腺的摄取。 Anti-Fas诱导后2 h时后,小鼠肝脏对99mTc-Annexin B1的摄取显著高于为对照动物的肝脏摄取。 结论 99mTc-Annexin B1具有与PS结合的体外生物活性和探测体内细胞凋亡的潜力,是一种新的细胞凋亡显像剂。 |
| 英文摘要: |
| Objective Annexin B1, a novel Ca2+-dependent phosphatidylserine (PS)-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells or activated platelets. The aim of this study was to develop and bioevaluate a Annexin B1 based PS-targeting radiotracer. Methods Annexin B1 was directly radiolabeled with technetium-99m using stannous chloride as reducing agent in the presence of citrate. Binding assay with human activated platelets was used to evaluate the biological activity of 99mTc-Annexin B1 in vitro. Biodistribution of this radioligand was studied in normal mice. The potential of 99mTc-Annexin B1 to detect apoptosisin vivo was evaluated in dexamethasone-inducecd thymus apoptotic mice and anti-Fas antibody induced liver apoptotic mice. Results The labeling procedure yielded 99mTc-Annexin B1 with high radiochemical purity and good in vitro stability. Platelets binding assay indicated that 99mTc-Annexin B1 retained its PS binding activity in vitro. 99mTc-Annexin B1 is rapidly cleared from the blood and predominantly accumulates in the kidney.The uptake of mouse thymus increased markedly at 18 hours after the administration of dexamethasone compared with control mice. Radionuclide imaging showed a markedly increased uptake of 99mTc-Annexin B1 in the liver of anti-Fas antibody treated mice compared with the control. Conclusion These data suggest that 99mTc-Annexin B1 retain its in vitro and in vivo biological activities. It may therefore be useful as a novel radioligand for the noninvasive imaging of PS externalization associated with apoptosis. |
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