The aim of this study was to investigate the capability of phenazine dioxides, recognized
bioreductive antitumour agents, as carriers for 99mTc in order to generate potential theranostic radiopharmaceuticals
towards hypoxic solid tumours.
Two different phenazine dioxides were used as ligands for the 99mTc-tricarbonyl core in order to prepare
the potential radiopharmaceuticals. The main physicochemical and biological properties were
evaluated. Biodistribution of the two radiotracers was studied at different time points after intravenous injection in tumour
Both compounds were obtained in high yield and radiochemichal purity. They were stable in labelling milieu, in human
plasma and in the presence of histidine. Biodistribution studies in mice were characterized by slow blood clearance and
persistent liver uptake, results that correlate with the values of lipophilicities and protein binding. Both the complexes
showed good tumour uptake, which remained constant during the studied period. Tumour/muscle ratios proved very favourable,
comparable to those of FMISO in the same animal model. On the other hand, tumour/blood ratios were low due
to high blood uptake.
The use of phenazine dioxides as ligands for the preparation of potential 99mTc-radiopharmaceuticals towards solid tumours
is possible since tumour uptake and retention are promising although high blood and liver uptake are drawbacks