Novel ^99mTc-Labeled Glucose Derivative for Single Photon Emission Computed Tomography: A Promising Tumor Imaging Agent

Abstract

In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with Tc for preparingTc-CN5DG. Tc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer demonstrated a positive response to the administration of glucose and insulin in S180 and A549 tumor cells in vitro, suggesting the mechanism of Tc-CN5DG into tumor cells was related to glucose transporters. Biodistribution studies in mice bearing A549 xenografts showedTc-CN5DG had a high tumor uptake and high tumor-to-background ratios. SPECT/CT images further supported its ability for tumor imaging. As a cheap, conveniently made and widely available probe, Tc-CN5DG would become a potential "working horse" and be a breakthrough inTc-labeled radiopharmaceuticals for tumor detection.

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

“…First, compound 4 was synthesized according to the published literature, [ 21 ] and the synthetic route was shown in Scheme 1. CN3DG ( 5 ) was synthesized as follows: d ‐glucosamine hydrochloride (117 mg, 0.54 mmol) and sodium hydroxide (22 mg, 0.54 mmol) were dissolved in methanol (20 ml) and stirred at room temperature for 30 min.…”

“…The cell uptake blocking studies were conducted according to the previous published literatures. [ 20,21 ] S180 cells were used for cell uptake studies; 3 × 10 6 cells were suspended in 0.5 ml of glucose‐free medium containing d ‐glucose (2 mg) or l ‐glucose (2 mg) (each group has five tubes) in 2‐ml centrifuge tubes. Then, [ 99m Tc(CN3DG) 6 ] + (0.5 ml, 740 kBq) or [ 99m Tc(CO) 3 (CN3DG) 3 ] + (0.5 ml, 740 kBq) was added, and the mixtures were incubated at 37°C for 4 h. After 4‐h incubation, the tubes were centrifuged and the supernatant were removed.…”

“…In our previous studies, a glucose derivative with an isonitrile group (CN5DG) was synthesized and radiolabeled with [ 99m Tc(I)] + core to prepare 99m Tc‐CN5DG. [ 21 ] 99m Tc‐CN5DG exhibited a certain tumor uptake and favorable blood and muscle clearance; however, its tumor uptake needs to be increased, and its initial blood uptake needs to be decreased to obtain better SPECT images. Bearing in mind the different 99m Tc cores, lipophilicity and overall size are the main factors influencing the biodistribution results of the resulting 99m Tc complexes [ 22–26 ] ; in this study, 4‐isocyano‐ N ‐(2,4,5‐trihydroxy‐6‐(hydroxymethyl)tetrahydro‐2 H ‐pyran‐3‐yl)butanamide (CN3DG) (Scheme 1) with less methylene number was synthesized and radiolabeled with [ 99m Tc(I)] + core and [ 99m Tc(I)(CO) 3 ] + core to obtain [ 99m Tc(CN3DG) 6 ] + and [ 99m Tc(CO) 3 (CN3DG) 3 ] + (Figure 1).…”

Nuclear Imaging of Glucose Metabolism: Beyond 18F-FDG

“…Recently, a D-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and labeled with 99m Tc to prepare 99m Tc-CN5DG (Figure 3) [40]. 99m Tc-CN5DG was readily obtained with high radiochemical purity (>95%) and specific activity (11.17–335.22 GBq/mmol).…”

“…Whole-body SPECT/CT images of 99m Tc-CN5DG (55 MBq) in nude mice bearing A549 xenografts with a tumor size of 3 mm (b) and 5 mm (c) in diameter at 30 min, 60 min, and 120 min after injection. Adapted from Reference [40] with permission.…”