99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study
99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study
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DOI：
10.1016/j.ejps.2015.05.002
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发表时间：
2015-08-30
影响因子：
4.6
通讯作者：
El-Mohty, A. A.
中科院分区：
文献类型：
--
作者：
Essa, B. M.;Sakr, T. M.;El-Mohty, A. A.
乳过氧化物酶(LPO)抑制剂对实体瘤有很高的选择性，因为它们与LPO酶有很高的结合亲和力。通过计算研究筛选出具有较高电子亲和力的顶级LPO抑制剂(单独或与~(99m)Tc-99m复配)。新制备的~(99m)Tc-氨基甲酸酯络合物在Si/ICO和体内对实体瘤均表现出较高的亲和力。以较高的放化产率(89.7+/-3.25)合成了TC-99M-氨基甲酸酯。其体外稳定性高达6h，在实体瘤小鼠体内的临床前评价表明，它在实体瘤细胞中有较高的滞留和生物蓄积，60min后靶向/非靶向(TINT)值高达4.9。上述数据表明，~(99m)Tc-氨基甲酸可作为实体瘤显像的潜在靶向显像剂。(C)2015爱思唯尔B.V.保留所有权利。
Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with Tc-99m) with high in silico affinity. The novel prepared Tc-99m-amitrole complex demonstrated both in si/ico and in vivo high affinity toward solid tumors. Tc-99m-amitrole was radio-synthesized with a high radiochemical yield (89.7 +/- 3.25). It showed in vitro stability for up to 6 h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (TINT) ratio equal to 4.9 at 60 min post-injection. The data described previously could recommend Tc-99m-amitrole as potential targeting scintigraphic probe for solid tumor imaging. (C) 2015 Elsevier B.V. All rights reserved.