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 ¹⁸ F-labeled positron emission tomography (PET) tracer, ¹⁸ F-2 , was prepared. PET/CT imaging studies demonstrated that ¹⁸ F-2 exhibited rapid brain uptake without significant wash out during the 60 min scanning time. In addition, the binding of ¹⁸ F-2 was higher in the regions of the brain stem, cerebellum, and midbrain. The uptake of ¹⁸ F-2 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.