Zn Complex of Diaminedithiol Tetradentate Ligand as a Stable Precursor for ^99mTc-Labeled Compounds

The diaminedithiol (N₂S₂) tetradentate ligand constitutes a useful chelating molecule for preparing ^99mTc-labeled compounds of high in vivo stability in high radiochemical yields. However, since the thiol groups in the N₂S₂ ligand are easy to be oxidized to disulfide bonds, they need to be protected with an appropriate protecting group, which hinders the broad applications of the N₂S₂ ligand for radiopharmaceuticals. In this study, a Zn chelate of N₂S₂ was evaluated as a precursor for purification-free ^99mTc-labeled N₂S₂ under the mild and simple procedure. Zn-N₂S₂ was prepared by reacting Zn acetate with N₂S₂, and the Zn-N₂S₂ remained stable under aerobic conditions at room temperature. ^99mTc-N₂S₂ was obtained over 90% radiochemical yields at room temperature by a one-pot reaction, consisting of Zn-N₂S₂ (10^-5 M), ^99mTcO₄^-, ethylenediaminetetraacetic acid (EDTA), and a reducing agent (Sn²⁺) at pH = 5.5 to 7.5. ^99mTc-N₂S₂ was also obtained over 90% radiochemical yields when the reaction was conducted in the presence of an equimolar amount of IgG antibody. These findings indicate the Zn complex of N₂S₂ ligand constitutes a stable and useful precursor to prepare ^99mTc-labeled N₂S₂ compounds in high yields under the mild and simple procedure.