Synthesis, radiolabeling and biological evaluation of butene amine oxime containing nitrotriazole as a tumor hypoxia marker
Synthesis, radiolabeling and biological evaluation of butene amine oxime containing nitrotriazole as a tumor hypoxia marker
复制标题
含硝基三唑的丁烯胺肟作为肿瘤缺氧标志物的合成、放射性标记及生物学评价
DOI：
10.1007/s41365-016-0028-3
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发表时间：
2016
影响因子：
2.8
通讯作者：
Chu Tai-Wei
中科院分区：
文献类型：
--
作者：
Zhang Qiang;Chu Tai-Wei
99mTc-BnAO, as a nonnitroaromatic hypoxia marker, is the subject of intensive research in recent years. In this study, a butene amine oxime–nitrotriazole (BnAO–NT) was synthesized and radiolabeled with99mTc in high yield. Cellular uptakes of99mTc-BnAO–NT and99mTc-BnAO were tested using murine sarcoma S180 and hepatoma H22 cell lines. The highest hypoxic cellular uptake of99mTc-BnAO–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. For99mTc-BnAO, 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. Both99mTc-BnAO–NT and99mTc-BnAO 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 BnAO complexes. The biodistribution study was tested using a S180 tumor model. The complex99mTc-BnAO–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 of99mTc-BnAO, the latter was at the same level. In vitro and in vivo studies demonstrated that99mTc-BnAO–NT could be a hypoxia-sensitive radiotracer for monitoring hypoxic regions in a sarcoma S180 tumor.
