BCPP compounds, PET probes for early therapeutic evaluations, specifically bind to mitochondrial complex I

Abstract

BCPP compounds have been developed as PET imaging probes for neurodegenerative diseases in the living brain. ¹⁸F-BCPP-EF identifies damaged neuronal areas based on the lack of MC-I; however, its underlying mechanisms of action and specificity for MC-I remain unclear. We herein report the effects of BCPP-BF, -EF, -EM on MC-I in respiratory chain complexes using cardiomyocyte SMP. BCPP compounds inhibited the binding of ³H-dihydrorotenone to MC-I and the proton pumping activity of MC-I in a concentration-dependent manner in vitro. These results suggest that BCPP compounds are MC-I selective inhibitors, and, thus, these radiolabeled compounds are useful for the quantitative imaging of MC-I using PET.

Keywords: BCPP compounds; Brain; Mitochondrial complex I; PET imaging probe; Positron emission tomography; Rotenone.