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

2-fluoro-2-deoxy-D-glucose (FDG) is considered of great interest. Herein,we present the synthesis and preliminary bioevaluation of a 99mTc(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-[99mTc(CO)3(H2O)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 (51%). Biodistribution in C57BL/6 mice bearing induced Lewis murine lung carcinoma is characterized by low blood and liver uptake and rapid urinary excretion. 99mTc 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 [18F]-FDG. However, tumour uptake was significantly higher for [18F]-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 linkermight improve biological results

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(LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)

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