Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake
Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake
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99mTc-BnAO 及其类似物的初步研究：合成、放射性标记和体外细胞摄取
DOI：
10.1016/j.nucmedbio.2009.09.003
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Wang, Xiangyun
中科院分区：
文献类型：
--
作者：
Sun, Xin;Chu, Taiwei;Wang, Xiangyun
简介：Tc-99m-BnAO 是引用率最高的非硝基咪唑缺氧标记物之一，可能在肿瘤学和其他临床应用中具有潜在用途。然而，由于绝对积累较低和缺氧/常氧摄取比较小，其在体外表现较差。 Tc-99m-BnAO的配体经过修饰后，Tc-99m-BnAO的类似物可能具有更高的缺氧选择性。方法：合成2,2'-(1,4-二氨基丁烷)双(2-甲基-3-丁酮)二肟(BnAO或HL91)和3种新型类似物，并用锝-99m进行放射性标记。在缺氧和常氧条件下测定小鼠肉瘤5180细胞系对放射性标记复合物的细胞摄取。结果：Tc-99m-BnAO及其三种新型类似物在缺氧细胞中持续积累，但在常氧细胞中不积累，而类似物表现出更早的缺氧选择性和更大的缺氧/常氧差异。结论：类似物在缺氧/常氧条件下优于Tc-99m-BnAO体外缺氧选择性的概念，并且是未来进一步开发作为新的非硝基咪唑缺氧标记物的可行候选者。 (C) 2010 Elsevier Inc. 保留所有权利。
Introduction: Tc-99m-BnAO is one of the nonnitroimidazole hypoxia markers with the highest citation and could be potentially useful in both oncology and other clinical applications. However, it appears inferior in vitro due to lower absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible that the analogues of Tc-99m-BnAO have higher hypoxia selectivity after the ligand of Tc-99m-BnAO is modified.Methods: 2,2'-(1,4-Diaminobutane)bis(2-methyl-3-butanone) dioxime (BnAO or HL91) and three novel analogues were synthesized and radiolabeled with technetium-99m. The cellular uptake of the radiolabeled complexes was determined in murine sarcoma 5180 cell lines under anoxic and normoxic conditions.Results: Tc-99m-BnAO and its three novel analogues continuously accumulated in anoxic cells but not in normoxic ones, while the analogues showed earlier hypoxia selectivity and greater anoxic/normoxic differential.Conclusions: The analogues are superior to Tc-99m-BnAO in terns of in vitro hypoxia selectivity and are viable candidates for further development as new nonnitroimidazole hypoxia markers in the future. (C) 2010 Elsevier Inc. All rights reserved.