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Novel Positron Emission Tomography Radiotracers for Imaging Mitochondrial Complex I

Year: 2021

Type: article

Abstract: 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.

Source: ACS Chemical Neuroscience

DOI: 10.1021/acschemneuro.1c00297