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

[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.