Evaluation of 6-11C-Methyl-m-Tyrosine as a PET Probe for Presynaptic Dopaminergic Activity: A Comparison PET Study with β-11C-l-DOPA and 18F-FDOPA in Parkinson Disease Monkeys.

We recently developed a novel PET probe, 6-(11)C-methyl-m-tyrosine ((11)C-6MemTyr), for quantitative imaging of presynaptic dopamine synthesis in the living brain. In the present study, (11)C-6MemTyr was compared with β-(11)C-l-DOPA and 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) in the brains of normal and Parkinson disease (PD) model monkeys (Macaca fascicularis). PD model monkeys were prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and (11)C-β-CFT was applied to assess neuronal damage as dopamine transporter (DAT) availability. (11)C-6MemTyr, β-(11)C-l-DOPA, or (18)F-FDOPA was injected with and without carbidopa, a specific inhibitor of peripheral aromatic L-amino acid decarboxylase. In normal and PD monkeys, the dopamine synthesis rates calculated using PET probes were analyzed by the correlation plot with DAT availability in the striatum. In normal monkeys, whole-brain uptake of β-(11)C-l-DOPA and (18)F-FDOPA were significantly increased by carbidopa at the clinical dose of 5 mg/kg by mouth. In contrast, (11)C-6MemTyr was not affected by carbidopa at this dose, and the metabolic constant value of (11)C-6MemTyr in the striatum was significantly higher than those of the other 2 PET probes. Significant reduction of the presynaptic DAT availability in the striatum was detected in MPTP monkeys, and correlation analyses demonstrated that (11)C-6MemTyr could detect dopaminergic damage in the striatum with much more sensitivity than the other PET probes. (11)C-6MemTyr is a potential PET probe for quantitative imaging of presynaptic dopamine activity in the living brain with PET.