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

We recently developed a novel PET probe, 6-¹¹C-methyl-m-tyrosine (¹¹C-6MemTyr), for quantitative imaging of presynaptic dopamine synthesis in the living brain. In the present study, ¹¹C-6MemTyr was compared with β-¹¹C-l-DOPA and 6-¹⁸F-fluoro-l-dopa (¹⁸F-FDOPA) in the brains of normal and Parkinson disease (PD) model monkeys (Macaca fascicularis). Methods: PD model monkeys were prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and ¹¹C-β-CFT was applied to assess neuronal damage as dopamine transporter (DAT) availability. ¹¹C-6MemTyr, β-¹¹C-l-DOPA, or ¹⁸F-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. Results: In normal monkeys, whole-brain uptake of β-¹¹C-l-DOPA and ¹⁸F-FDOPA were significantly increased by carbidopa at the clinical dose of 5 mg/kg by mouth. In contrast, ¹¹C-6MemTyr was not affected by carbidopa at this dose, and the metabolic constant value of ¹¹C-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 ¹¹C-6MemTyr could detect dopaminergic damage in the striatum with much more sensitivity than the other PET probes. Conclusion: ¹¹C-6MemTyr is a potential PET probe for quantitative imaging of presynaptic dopamine activity in the living brain with PET.

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