PET Imaging of Mitochondrial Complex I with 18F-BCPP-EF in the Brains of MPTP-Treated Monkeys

Unlabelled: (18)F-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: (11)C-β-CFT for the dopamine transporter; (11)C-3,4-dihydroxy-phenyl-L-alanine (β-(11)C-L-DOPA), L-6-(18)F-fluorodopa ((18)F-FDOPA), or 6-(11)C-methyl-m-tyrosine ((11)C-6MemTyr) for dopamine synthesis; or 2-tert-butyl-4-chrolo-5-{6-[2-(2-(18)F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ((18)F-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 (11)C-6MemTyr >> β-(11)C-L-DOPA > (18)F-FDOPA.

Conclusion: (18)F-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.