Preparation and bioevaluation of 99mTc-HYNIC-annexin B1 as a novel radioligand for apoptosis imaging
Preparation and bioevaluation of 99mTc-HYNIC-annexin B1 as a novel radioligand for apoptosis imaging
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DOI：
10.1007/s10495-008-0189-6
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发表时间：
2008-02
期刊：
影响因子：
7.2
通讯作者：
Quan-Yong Luo;F. Wang;Zhi‐Yong Zhang;Yi Zhang;Hankui Lu;Shuhan Sun;R. Zhu
中科院分区：
文献类型：
--
作者：
Quan-Yong Luo;F. Wang;Zhi‐Yong Zhang;Yi Zhang;Hankui Lu;Shuhan Sun;R. Zhu
膜联蛋白B1是一种新型的钙离子依赖性PS结合蛋白，对凋亡细胞表面的PS具有高度的亲和力。为了开发和生物评价基于膜联蛋白B1的PS靶向放射性示踪剂，使用HYNIC作为双功能螯合剂，用99 mTc放射性标记膜联蛋白B1。用活化血小板和凋亡的SP2/0细胞进行结合试验，以评价99 mTc-HYNIC-annexin B1的体外生物学活性。在正常小鼠中研究了该放射性配体的生物分布。地塞米松诱导的小鼠胸腺细胞凋亡和Fas介导的小鼠肝细胞凋亡模型，用于研究放射性标记的膜联蛋白B1在体内检测细胞凋亡的能力。标记过程产生的化合物具有高达98%的放射化学纯度和良好的体外稳定性。体外结合实验表明，99 mTc-HYNIC-annexin B1保留了PS结合活性。该化合物在小鼠体内的生物分布表明，99 mTc-HYNIC-annexin B1从血液中迅速清除，并主要蓄积在肾脏中。地塞米松处理的小鼠胸腺摄取和Fas介导的小鼠肝脏摄取的显著增加与细胞凋亡的组织学证据相关。这些结果表明，99 mTc-HYNIC-annexin B1在体外和体内均具有生物学活性。因此，这种放射性示踪剂可能是有用的，作为一种新的放射性配体的非侵入性检测PS外化与凋亡。
Annexin B1, a novel Ca2+-dependent PS-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells. To develop and bioevaluate an annexin B1 based PS-targeting radiotracer, annexin B1 was radiolabeled with99mTc using HYNIC as a bifunctional chelator. Binding assays with activated platelets and apoptotic SP2/0 cells were carried out to evaluate the in vitro biological activity of99mTc-HYNIC-annexin B1. Biodistribution of this radioligand was studied in normal mice. Dexamethasone-induced murine thymus apoptosis and fas-mediated murine liver apoptosis models were used to investigate the ability of radiolabeled annexin B1 to detect apoptosis in vivo. The labeling procedure yielded a compound with up to 98% radiochemical purity and good in vitro stability. The in vitro binding assays indicated that99mTc-HYNIC-annexin B1 retain its PS-binding activity. Biodistribution of the compound in mice showed that99mTc-HYNIC-annexin B1 is rapidly cleared from the blood and predominantly accumulates in the kidney. The marked increase in dexamethasone-treated murine thymus uptake and fas-mediated murine liver uptake correlated with histologic evidence of apoptosis. These data suggested that99mTc-HYNIC-annexin B1 retain its in vitro and in vivo biological activities. This radiotracer may therefore be useful as a novel radioligand for the noninvasive detecting of PS externalization associated with apoptosis.