RT Journal Article
SR Electronic
T1 Evaluation of 6-<sup>11</sup>C-Methyl-<em>m</em>-Tyrosine as a PET Probe for Presynaptic Dopaminergic Activity: A Comparison PET Study with β-<sup>11</sup>C-<span class="sc">l</span>-DOPA and <sup>18</sup>F-FDOPA in Parkinson Disease Monkeys
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 303
OP 308
DO 10.2967/jnumed.115.161802
VO 57
IS 2
A1 Masakatsu Kanazawa
A1 Hiroyuki Ohba
A1 Norihiro Harada
A1 Takeharu Kakiuchi
A1 Shin-ichi Muramatsu
A1 Hideo Tsukada
YR 2016
UL http://jnm.snmjournals.org/content/57/2/303.abstract
AB 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.