Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia
Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia
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DOI：
10.1039/c5md00042d
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Zhenxiang Li;Junbo Zhang;Zhong-hui Jin;Weifang Zhang;Yan-yan Zhang
中科院分区：
文献类型：
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作者：
Zhenxiang Li;Junbo Zhang;Zhong-hui Jin;Weifang Zhang;Yan-yan Zhang
合成了 3-(4-硝基-1H-咪唑基)丙基二硫代氨基甲酸钠 (N4IPDTC)，并用 [99mTcO]3+、[99mTcN]2+ 或 [99mTc(CO)3]+ 核心进行放射性标记，生成 99mTcO-N4IPDTC、99mTcN-N4IPDTC 和 分别为 99mTc(CO)3-N4IPDTC。所有三种配合物均具有高放射化学纯度，并且在 6 小时内具有良好的体外稳定性。分配系数结果表明99mTcO-N4IPDTC和99mTcN-N4IPDTC具有亲脂性，而99mTc(CO)3-N4IPDTC具有亲水性。肿瘤细胞实验和荷S180肿瘤小鼠体内的生物分布表明，所有复合物均表现出良好的缺氧选择性和在肿瘤中的积累。其中，99mTcO-N4IPDTC具有较高的肿瘤摄取率、较高的肿瘤/血液比和肿瘤/肌肉比等优点。平面闪烁扫描成像研究表明，肿瘤部位有明显的积累，表明其作为肿瘤缺氧成像剂的潜在用途。
Sodium 3-(4-nitro-1H-imidazolyl)propyl dithiocarbamate (N4IPDTC) was synthesized and radiolabelled with a [99mTcO]3+, [99mTcN]2+ or [99mTc(CO)3]+ core to produce 99mTcO-N4IPDTC, 99mTcN-N4IPDTC and 99mTc(CO)3-N4IPDTC, respectively. All of the three complexes were prepared with high radiochemical purity and had good in vitro stability over a period of 6 h. The partition coefficient results showed that 99mTcO-N4IPDTC and 99mTcN-N4IPDTC were lipophilic, while 99mTc(CO)3-N4IPDTC was hydrophilic. The tumor cell experiments and the biodistribution in mice bearing S180 tumors showed that all of the complexes exhibited good hypoxic selectivity and accumulation in the tumor. Among them, 99mTcO-N4IPDTC had the advantages of higher tumor uptake, and higher tumor/blood and tumor/muscle ratios. Planar scintigraphic imaging studies showed there was a visible accumulation in tumor sites, suggesting its potential usefulness as a tumor hypoxia imaging agent.