Macrocyclic triamine derived glucose analogues for Tc-99m(CO)(3) labeling: synthesis and biological evaluation as potential tumor-imaging agents

作者：Liu, Teli; Gan, Qianqian; Zhang, Junbo^*

来源：Chemical Biology & Drug Design, 2017, 89(2): 277-284.

DOI：10.1111/cbdd.12784

• Tc-99m(CO)(3)
• biodistribution
• click chemistry
• glucose analogue
• macrocyclic triamine
• tumor-imaging agent

[Tc-99m(CO)(3)(H2O)(3)](+) has attracted great attention among Tc-99m-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[Tc-99m(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 [Tc-99m(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] aneN(3) via the so-called click chemistry and radiolabeled with [Tc-99m(CO)(3)(H2O)(3)](+) to form Tc-99m(CO) 3-6 (C-1-substituted complex) and Tc-99m(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 degrees 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, Tc-99m(CO)(3)-7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported Tc-99m-radiolabeled glucose derivatives, Tc-99m(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.

• 出版日期2017-2
• 单位北京师范大学