Evaluation and comparison of 99mTc‐labeled d‐glucosamine derivatives with different 99mTc cores as potential tumor imaging agents

Abstract

Isocyanide is a strong coordination ligand that can coordinate with [99mTc(I)(CO)3]+ core and [99mTc(I)]+ core to produce stable 99mTc complexes, therefore developing a 99mTc‐labeled isocyanide complex for single‐photon emission computed tomography (SPECT) imaging is considered to be of great interest. In order to develop potential tumor imaging agents with satisfied tumor uptake and suitable pharmacokinetic properties in vivo, a novel d‐glucosamine isocyanide derivative, 4‐isocyano‐N‐(2,4,5‐trihydroxy‐6‐(hydroxymethyl)tetrahydro‐2H‐pyran‐3‐yl)butanamide (CN3DG), was synthesized and radiolabeled with [99mTc(I)]+ and [99mTc(CO)3]+ cores to obtain [99mTc(CN3DG)6]+ and [99mTc(CO)3(CN3DG)3]+ in high radiolabeling yields (>95%). Both of the complexes showed good hydrophilicity and great stability in vitro. Cell uptake studies performed in S180 cells demonstrated they were transported into cells by glucose transporters. Biodistribution studies of the two complexes in mice bearing S180 tumor showed they had high tumor uptakes and rapid clearance from muscle and blood so that the tumor/blood and tumor/muscle ratios were high. By comparison, [99mTc(CN3DG)6]+ was superior to [99mTc(CO)3(CN3DG)3]+ in regard to tumor uptake, tumor/blood and tumor/liver ratios. S180 tumors could be seen clearly from the SPECT/CT images with [99mTc(CN3DG)6]+. Considering its favorable properties, [99mTc(CN3DG)6]+ would be a promising tumor imaging agent and needs to be further studied.