Macrocyclic triamine derived glucose analogues for ^99m Tc(CO)₃ labeling: synthesis and biological evaluation as...

[^99m Tc(CO)₃ (H₂ O)₃ ]⁺ has attracted great attention among ^99m Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[^99m Tc(CO)₃ (H₂ O)₃ ]⁺ by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [^99m Tc(CO)₃ (H₂ O)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 [^99m Tc(CO)₃ (H₂ O)₃ ]⁺ to form ^99m Tc(CO)₃ -6 (C-1-substituted complex) and ^99m Tc(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, ^99m Tc(CO)₃ -7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported ^99m Tc-radiolabeled glucose derivatives, ^99m Tc(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.