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。
Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake.
机构信息
Beijing National Laboratory for Molecular Sciences (BNLMS), Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
出版信息
Nucl Med Biol. 2010 Feb;37(2):117-23. doi: 10.1016/j.nucmedbio.2009.09.003. Epub 2009 Nov 3.
INTRODUCTION
(99m)Tc-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 (99m)Tc-BnAO have higher hypoxia selectivity after the ligand of (99m)Tc-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 S180 cell lines under anoxic and normoxic conditions.
RESULTS
(99m)Tc-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 (99m)Tc-BnAO in terms of in vitro hypoxia selectivity and are viable candidates for further development as new nonnitroimidazole hypoxia markers in the future.
简介
（99m）Tc-BnAO 是引用率最高的非硝基咪唑类乏氧标志物之一，有望在肿瘤学和其他临床应用中得到应用。然而，由于绝对摄取量较低和乏氧/常氧摄取比值较小，其在体外表现不佳。（99m）Tc-BnAO 的配体修饰后，类似物可能具有更高的缺氧选择性。
方法
合成了 2,2'-(1,4-二氨基丁烷)双(2-甲基-3-丁酮)二肟（BnAO 或 HL91）和三种新型类似物，并将其用锝-99m 标记。在乏氧和常氧条件下，测定了放射性标记配合物在小鼠肉瘤 S180 细胞系中的细胞摄取。
结果
（99m）Tc-BnAO 及其三种新型类似物在乏氧细胞中持续积累，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乏氧/常氧差异。
结论
这些类似物在体外缺氧选择性方面优于（99m）Tc-BnAO，是作为未来新型非硝基咪唑类乏氧标志物进一步开发的候选药物。
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