Immobilization of the Gas Signaling Molecule H₂S by Radioisotopes: Detection, Quantification, and In Vivo Imaging

Hydrogen sulfide (H₂S) has multifunctional roles as a gas signaling molecule in living systems. However, the efficient detection and imaging of H₂S in live animals is very challenging. Herein, we report the first radioisotope-based immobilization technique for the detection, quantification, and in vivo imaging of endogenous H₂S. Macrocyclic⁶⁴Cu complexes that instantly reacted with gaseous H₂S to form insoluble⁶⁴CuS in a highly sensitive and selective manner were prepared. The H₂S concentration in biological samples was measured by a thin-layer radiochromatography method. When⁶⁴Cu–cyclen was injected into mice, an elevated H₂S concentration in the inflamed paw was clearly visualized and quantified by Cerenkov luminescence and positron emission tomography (PET) imaging. PET imaging was also able to pinpoint increased H₂S levels in a millimeter-sized infarcted lesion of the rat heart.