PET imaging of mitochondrial complex i with 18F-BCPP-EF in the brains of MPTP-treated monkeys

Abstract

18F-BCPP-EF was applied to assess mitochondrial complex I (MC-I) activity in the brains of Parkinson disease model monkeys prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and also presynaptic dopamine parameters. Methods: 11C-β-CFT for the dopamine transporter; 11C-3,4-dihydroxy-phenyl-L-alanine (β-11CL- DOPA), L-6-18F-fluorodopa (18F-FDOPA), or 6-11C-methyl-m-tyrosine (11C-6MemTyr) for dopamine synthesis; or 2-tert-butyl-4-chrolo- 5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin- 3-one (18F-BCPP-EF) for MC-I was intravenously injected into normal and MPTP monkeys in order to analyze their uptake in the striatum. Results: Significant reductions in presynaptic dopamine parameters and MC-I activity were detected in the striatum of MPTP monkeys. Correlations were observed between MC-I activity and dopamine transporter as well as between MC-I activity and dopamine synthesis in the striatum. The order of detectability of impaired MC-I activity was 11C-6MemTyr > > β-11C-L-DOPA > 18F-FDOPA. Conclusion: 18F-BCPP-EF has potential as a PET probe for the quantitative imaging of MC-I damage in the living brains of Parkinson disease model monkeys using PET.