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The chemical structure of (99m)Tc-GSH has been estabilished using the (99)Tc isotope. Labeling of glutathione with technetium in the presence of stanous chloride gave a high yield result. In a comparative study between (99)Tc and (99)Tc glutathione, the Tc-GSH complex obtained was purified and characterized by uv, visible spectroscopy, HPLC, Biogel chromatography, mass and NMR spectroscopy. Stoichiometric analysis showed a 2 : 1 molar ratio of GSH/Tc for the reaction. The molecular mass assessed by mass spectroscopy was 727 Da corresponding to an oxo(bis) glutathione technetate. NMR studies demonstrated that each glutathione molecule was coordinated to technetium via cysteinyl sulfur and nitrogen atoms. The biodistribution of the complex was studied in normal rats. Blood clearance was rapid during the first hour involving a biexponential curve ( t1/2 (1) : 50 min, t1/2 (2) : 400 min ). No radioactive accumulation was found in any specific organ except kidney and bladder. All the activity excreted was found unchanged in urine. In conclusion, Tc-GSH displayed an anionic dimer form as GSH-Tc-GSH. We assume that the complex is a tetradentate (2N,2S) complex containing a pentavalent technetium coordinated by two thiol and nitrogen atoms of both GSH ligands, and an apical oxo group.

Tc-Glutathione Complex (Tc -GSH) : Labelling, Chemical Characterization and Biodistribution in Rats