Preparation and preliminary bioevaluation of a 99mTc(CO)3‐glucose derivative prepared by a click chemistry route

Development of a 99m Tc‐labelled glucose derivative as a single‐photon emission computed tomography analogue to [ 18 F]‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) is considered of great interest. Herein, we present the synthesis and preliminary bioevaluation of a 99m Tc(CO) 3 ‐glucose derivative. Derivatization of glucose at C2 was achieved using the so‐called ‘click chemistry’, forming a histidine‐like, 1,4‐disubstituted triazole adequate as donor atom system for Tc(I)‐tricarbonyl complexes. Synthesis of the intermediate azide derivative was achieved by conventional organic chemistry. Because of the efficiency and selectivity of this cycloaddition, labelling was performed in ‘one pot’, adding the tricarbonyl precursor fac ‐[ 99m Tc(CO) 3 (H 2 O) 3 ] + to the same vial where the click reaction has taken place without any further purification. A single product with radiochemical purity higher than 90% was obtained. It was stable for at least 4 h in reaction milieu and exhibited high hidrophilicity (log P of −1.2) and low binding to plasma proteins (5 ± 1%). Biodistribution in C57BL/6 mice bearing induced Lewis murine lung carcinoma is characterized by low blood and liver uptake and rapid urinary excretion. 99m Tc complex showed moderate tumour uptake but significant retention until 2 h post‐injection. Soft tissue clearance was fast leading to significantly higher uptake in tumour in comparison to muscle ( p = 0.05) at all time points. Overall, biodistribution of our compound was very similar to that of [ 18 F]‐FDG. However, tumour uptake was significantly higher for [ 18 F]‐FDG, probably because of high hidrophilicity of our derivative that may hinder cell penetration. Similarity to biodistribution of FDG is a promising outcome, and modifications of the chelator and linker might improve biological results. Copyright © 2012 John Wiley & Sons, Ltd.