含硝三唑的丙烯胺肟配合物的合成、放射性标记及作为缺氧标志物的生物学评价。
Synthesis, radiolabeling and biological evaluation of propylene amine oxime complexes containing nitrotriazoles as hypoxia markers.
机构信息
Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
出版信息
Molecules. 2012 Jun 4;17(6):6808-20. doi: 10.3390/molecules17066808.
Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4-triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 ± 0.2% and 35.0 ± 0.7% at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 ± 1.6% and 4.6 ± 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant anoxic/normoxic differentials. The cellular uptakes were highly dependent on oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At 4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1 and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second nitrotriazole redox center, the hypoxic accumulation of the marker was slightly enhanced.
两种丙烯亚胺肟（PnAO）配合物 1 和 2 被合成并标记高放化产率的（99m）Tc。用 S180 细胞系测试了（99m）Tc-1 和（99m）Tc-2 的细胞摄取。在缺氧条件下，（99m）Tc-1 和（99m）Tc-2 在 4 h 时的细胞摄取率分别为 33.7±0.2%和 35.0±0.7%，而在正常氧条件下，两种复合物的摄取率分别为 6.0±1.6%和 4.6±0.9%。（99m）Tc-1 和（99m）Tc-2 均显示出明显的缺氧/正常氧差异。细胞摄取高度依赖于氧气和温度。生物分布研究表明，（99m）Tc-1 和（99m）Tc-2 均选择性地在肿瘤中定位，并缓慢从肿瘤中清除。在 4 h 时，肿瘤/肌肉比值（T/M）分别为（99m）Tc-1 的 3.79 和（99m）Tc-2 的 4.58。这些结果表明，（99m）Tc 标记的 PnAO 配合物（99m）Tc-1 和（99m）Tc-2 可能作为新型缺氧标志物。通过引入第二个硝三唑氧化还原中心，标记物的缺氧积累略有增强。
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