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. Macrocyclic Cu-64 complexes that instantly reacted with gaseous H2S to form insoluble (CuS)-Cu-64 in a highly sensitive and selective manner were prepared. The H2S concentration in biological samples was measured by a thin-layer radiochromatography method. When Cu-64-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.