Imaging of the third gasotransmitter hydrogen sulfide using Tc-labeled alpha-hydroxy acids.

Introduction: Hydrogen sulfide (HS) defined as the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO) is an important mediator of various physiological functions. Although various HS-imaging techniques using fluorescence and luminescence have been developed, only one radionuclide imaging using Cu-labeled cyclen complex was reported. Thus, we tried to develop Tc-labeled HS imaging agents.

Methods: Various α-hydroxy acids such as glycolate, L-lactate, D-lactate, D-gluconate, D-glucoheptonate, D-glucuronate, D-glucarate, and citrate were labeled with Tc in the presence of stannous chloride. The labeled compounds were incubated with 0.2 mM of NaHS, and reactive sulfur species and then analyzed by ITLC/normal saline to detect the formation of insoluble complex. Matrigels containing various concentrations of NaHS were xenografted on the shoulder of normal mice, and an imaging study was performed after intravenous injection of [Tc]Tc-gluconate. We also obtained autoradiography image of a rat brain with a temporary brain ischemia after intravenous injection of [Tc]Tc-gluconate.

Results: [Tc]Tc-gluconate showed the highest formation of insoluble complex (87.8 ± 3.6%) after incubation with 0.2 mM NaHS. The other reactive species such as glutathione, cysteine, sulfite, sulfate, thiosulfate, and NO did not form insoluble complex representing the reaction being specific to HS. The Matrigel containing 2 μmol NaHS showed uptake of [Tc]Tc-gluconate, which proved the feasibility as the specific HS imaging agent in vivo. Temporary ischemic lesion of rat brain showed high radioactivity accumulation representing the feasibility as endogenous HS imaging agents.

Conclusion: We proved that Tc-labeled α-hydroxy acid especially [Tc]Tc-gluconate is a novel endogenous HS imaging agent, which might contribute to study and diagnosis of various diseases related with inflammation and hypoxia.