Synthesis, radiolabeling and biological evaluation of butene amine oxime containing nitrotriazole as a tumor hypoxia marker  

作　　者：Qiang Zhang Tai-Wei Chu 

机构地区：[1]Beijing National Laboratory for Molecular Sciences,Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University

出　　处：《Nuclear Science and Techniques》2016年第2期35-43,共9页核技术（英文）

基　　金：supported by the National Natural Science Foundation of China (Grant Nos. 21371017 and 81371592)

摘　　要：^(99m)Tc-BnAO, as a nonnitroaromatic hypoxia marker, is the subject of intensive research in recent years. In this study, a butene amine oxime–nitrotriazole(Bn AO–NT)was synthesized and radiolabeled with ^(99m)Tc in high yield.Cellular uptakes of^(99m)Tc-Bn AO–NT and ^(99m)Tc-Bn AO were tested using murine sarcoma S180 and hepatoma H22 cell lines. The highest hypoxic cellular uptake of^(99m)TcBn AO–NT was 27.11 ± 0.73 and 14.85 ± 0.83 % for the S180 and H22 cell lines, respectively, whereas the normoxic cellular uptake of the complex was about 4–8 % for both cell lines. For^(99m)Tc-Bn AO, the highest hypoxic cellular uptake was 30.79 ± 0.44 and 9.66 ± 1.20 % for the S180 and H22 cell lines, respectively, while the normoxic cellular uptake was about 5 % for both cell lines. Both^(99m)Tc-Bn AO–NT and^(99m)Tc-Bn AO complexes showed hypoxic/normoxic differentials in the two cell lines, but the results were more significant for the S180 cell line. The in vitro results suggested that S180 may be better than H22 cell line in hypoxic biological evaluation of Bn AO complexes. The biodistribution study was tested using a S180 tumor model. The complex^(99m)Tc-Bn AO–NT showed a selective enrichment in tumor tissues: At 4 h, the tumor-to-muscle ratio was 3.79 ± 0.98 and the tumor-to-blood ratio was 2.31 ± 0.34.Compared with the results of ^(99m)Tc-Bn AO, the latter was at the same level. In vitro and in vivo studies demonstrated that ^(99m)Tc-Bn AO–NT could be a hypoxia-sensitive radiotracer for monitoring hypoxic regions in a sarcoma S180 tumor.^（99m）Tc-BnAO, as a nonnitroaromatic hypoxia marker, is the subject of intensive research in recent years. In this study, a butene amine oxime–nitrotriazole（Bn AO–NT）was synthesized and radiolabeled with ^（99m）Tc in high yield.Cellular uptakes of^（99m）Tc-Bn AO–NT and ^（99m）Tc-Bn AO were tested using murine sarcoma S180 and hepatoma H22 cell lines. The highest hypoxic cellular uptake of^（99m）TcBn AO–NT was 27.11 ± 0.73 and 14.85 ± 0.83 % for the S180 and H22 cell lines, respectively, whereas the normoxic cellular uptake of the complex was about 4–8 % for both cell lines. For^（99m）Tc-Bn AO, the highest hypoxic cellular uptake was 30.79 ± 0.44 and 9.66 ± 1.20 % for the S180 and H22 cell lines, respectively, while the normoxic cellular uptake was about 5 % for both cell lines. Both^（99m）Tc-Bn AO–NT and^（99m）Tc-Bn AO complexes showed hypoxic/normoxic differentials in the two cell lines, but the results were more significant for the S180 cell line. The in vitro results suggested that S180 may be better than H22 cell line in hypoxic biological evaluation of Bn AO complexes. The biodistribution study was tested using a S180 tumor model. The complex^（99m）Tc-Bn AO–NT showed a selective enrichment in tumor tissues： At 4 h, the tumor-to-muscle ratio was 3.79 ± 0.98 and the tumor-to-blood ratio was 2.31 ± 0.34.Compared with the results of ^（99m）Tc-Bn AO, the latter was at the same level. In vitro and in vivo studies demonstrated that ^（99m）Tc-Bn AO–NT could be a hypoxia-sensitive radiotracer for monitoring hypoxic regions in a sarcoma S180 tumor.

关 键 词：细胞缺氧 肿瘤模型 生物学评价 标记 合成 胺肟 丁烯 S180 

分 类 号：R914.5[医药卫生—药物化学] R96[医药卫生—药学]