Macrocyclic triamine derived glucose analogues for 99mTc(CO)3 labeling: synthesis and biological evaluation as potential tumor-imaging agents
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- 作者：Teli Liu ; Qianqian Gan and Junbo Zhang
- 刊名：Chemical Biology & Drug Design
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：89
- 期：2
- 页码：277-284
- 全文大小：469K
- ISSN：1747-0285
文摘
[99mTc(CO)3(H2O)3]+ has attracted great attention among 99mTc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[99mTc(CO)3(H2O)3]+ by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [99mTc(CO)3(H2O)3]+ to produce stable complex. In this study, two novel 1, 5, 9-triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose-azides with alkyne-[12]aneN3 via the so-called click chemistry and radiolabeled with [99mTc(CO)3(H2O)3]+ to form 99mTc(CO)3-6 (C-1-substituted complex) and 99mTc(CO)3-7 (C-2-substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99mTc(CO)3-7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99mTc-radiolabeled glucose derivatives, 99mTc(CO)3-7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor-imaging agent.