Preparation and biological evaluation of (99m)Tc-labelled phenazine dioxides as potential tracers for hypoxia imaging

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Oncology

Background:

• Phenazine dioxides are known bioreductive antitumour agents.
• Development of theranostic radiopharmaceuticals for hypoxic solid tumours is an active area of research.
• Technetium-99m (99mTc) is a widely used radionuclide for diagnostic imaging and therapy.

Purpose of the Study:

• To evaluate phenazine dioxides as ligands for 99mTc-tricarbonyl core to create novel radiopharmaceuticals.
• To assess the physicochemical and biological properties of the resulting 99mTc-labelled compounds.
• To investigate their potential for theranostic applications in hypoxic solid tumours.

Main Methods:

• Synthesis and characterization of two 99mTc-labelled phenazine dioxide complexes.
• Evaluation of radiochemical purity, stability in vitro (plasma, histidine), and labelling milieu.
• In vivo biodistribution studies in tumour-bearing mice at various time points post-injection.

Main Results:

• High yields and radiochemical purity were achieved for both complexes.
• Compounds demonstrated stability in plasma and histidine, indicating good in vivo stability.
• Biodistribution showed slow blood clearance, persistent liver uptake, and promising, stable tumour uptake.
• Favourable tumour/muscle ratios were observed, comparable to FMISO, but tumour/blood ratios were low due to high blood retention.

Conclusions:

• Phenazine dioxides are viable ligands for developing 99mTc-based radiopharmaceuticals for solid tumours.
• Promising tumour uptake and retention suggest theranostic potential.
• High blood and liver uptake represent significant drawbacks that need to be addressed in future development.