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

详细信息    查看全文

• 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

[<sup>99msup>Tc(CO)<sub>3sub>(H<sub>2sub>O)<sub>3sub>]<sup>+sup> has attracted great attention among <sup>99msup>Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[<sup>99msup>Tc(CO)<sub>3sub>(H<sub>2sub>O)<sub>3sub>]<sup>+sup> by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [<sup>99msup>Tc(CO)<sub>3sub>(H<sub>2sub>O)<sub>3sub>]<sup>+sup> 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<sub>3sub> via the so-called click chemistry and radiolabeled with [<sup>99msup>Tc(CO)<sub>3sub>(H<sub>2sub>O)<sub>3sub>]<sup>+sup> to form <sup>99msup>Tc(CO)<sub>3sub>-6 (C-1-substituted complex) and <sup>99msup>Tc(CO)<sub>3sub>-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, <sup>99msup>Tc(CO)<sub>3sub>-7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported <sup>99msup>Tc-radiolabeled glucose derivatives, <sup>99msup>Tc(CO)<sub>3sub>-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.