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

[ 99m Tc( CO ) 3 (H 2 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 (H 2 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 (H 2 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]aneN 3 via the so‐called click chemistry and radiolabeled with [ 99m Tc( CO ) 3 (H 2 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.