Novel Positron Emission Tomography Radiotracers for Imaging Mitochondrial Complex I

Mitochondrial dysfunction has been indicated in neurodegenerative and other disorders. The mitochondrial complex I (MC-I) of the electron transport chain (ETC) on the inner membrane is the electron entry point of the ETC and is essential for the production of reactive oxygen species. Based on a recently identified β-keto-amide type MC-I modulator from our laboratory, an ¹⁸F-labeled positron emission tomography (PET) tracer, , was prepared. PET/CT imaging studies demonstrated that exhibited rapid brain uptake without significant wash out during the 60 min scanning time. In addition, the binding of was higher in the regions of the brain stem, cerebellum, and midbrain. The uptake of can be significantly blocked by its parent compound. Collectively, the results strongly suggest successful development of MC-I PET tracers from this chemical scaffold that can be used in future mitochondrial dysfunction studies of the central nervous system.