99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia
99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia
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99mTc 标记的塞克硝唑黄原酸盐复合物：作为针对肿瘤缺氧的潜在放射性示踪剂的合成和评估
DOI：
10.1016/j.apradiso.2018.07.036
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发表时间：
2018-10-01
影响因子：
1.6
通讯作者：
Zhang, Junbo
中科院分区：
文献类型：
--
作者：
Lin, Xiao;Ruan, Qing;Zhang, Junbo
在这项研究中，市售的塞克硝唑成功地转化为塞克硝唑黄原酸酯（SNXT），其中黄原酸酯基团可以作为双功能螯合剂与Tc-99 m配位。制备了高放化纯度的~（99 m）Tc-SNXT的氮代配合物（（TcN）-~（99 m）Tc-SNXT）和~（99 m）Tc-SNXT的氧代配合物（（TcO）-~（99 m）Tc-SNXT）。这两种复合物被发现是稳定的，在体外表现出相似的亲水性。此外，在缺氧和常氧条件下的体外细胞摄取的比较研究表明，这两种药物优先采取了缺氧细胞。在荷S180肿瘤小鼠体内的生物分布研究表明，（TcO）-Tc-99 m-SNXT的肿瘤摄取和肿瘤-肌肉比高于（TcN）-Tc-99 m-SNXT。在SPECT显像中，（TcO）-Tc-99 m-SNXT在肿瘤内有明显的蓄积，提示其可能成为一种新型的乏氧显像剂。
In this study, the commercially available secnidazole was successfully converted to secnidazole xanthate (SNXT), in which the xanthate group can act as a bifunctional chelator to coordinate with Tc-99m. Tc-99m-nitrido complex of SNXT((TcN)-Tc-99m-SNXT) and Tc-99m-oxo complex of SNXT((TcO)-Tc-99m-SNXT) were prepared with high radiochemical purity. Both of the complexes were found to be stable in vitro and to exhibit similar hydrophilicity. In addition, comparative in vitro cell uptake studies under anoxic and normoxic conditions demonstrated that both agents were preferentially taken up by hypoxic cells. Biodistribution studies in mice bearing S180 tumor showed (TcO)-Tc-99m-SNXT exhibited a higher tumor uptake and tumor-to-muscle ratio than (TcN)-Tc-99m-SNXT. Furthermore, in SPECT imaging study, (TcO)-Tc-99m-SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting its potential to be a novel hypoxia imaging agent.