Kanazawa Masakatsu, Ohba Hiroyuki, Harada Norihiro, Kakiuchi Takeharu, Muramatsu Shin-Ichi, Tsukada Hideo
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; and.
Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
J Nucl Med. 2016 Feb;57(2):303-8. doi: 10.2967/jnumed.115.161802. Epub 2015 Nov 12.
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.
我们最近开发了一种新型正电子发射断层扫描（PET）探针，即6-(11)C-甲基-m-酪氨酸（(11)C-6MemTyr），用于在活体大脑中对突触前多巴胺合成进行定量成像。在本研究中，将(11)C-6MemTyr与β-(11)C-L-多巴和6-(18)F-氟-L-多巴（(18)F-FDOPA）在正常和帕金森病（PD）模型猴（食蟹猴）大脑中进行了比较。
通过给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）制备PD模型猴，并应用(11)C-β-CFT评估神经元损伤，即多巴胺转运体（DAT）可用性。在有和没有外周芳香族L-氨基酸脱羧酶特异性抑制剂卡比多巴的情况下，注射(11)C-6MemTyr、β-(11)C-L-多巴或(18)F-FDOPA。在正常和PD猴中，使用PET探针计算的多巴胺合成率通过与纹状体中DAT可用性的相关图进行分析。
在正常猴中，口服5mg/kg临床剂量的卡比多巴可使β-(11)C-L-多巴和(18)F-FDOPA的全脑摄取显著增加。相比之下，该剂量的卡比多巴对(11)C-6MemTyr没有影响，且(11)C-6MemTyr在纹状体中的代谢常数显著高于其他两种PET探针。在MPTP猴中检测到纹状体中突触前DAT可用性显著降低，相关性分析表明，(11)C-6MemTyr比其他PET探针能更灵敏地检测纹状体中的多巴胺能损伤。
(11)C-6MemTyr是一种潜在的PET探针，可用于通过PET对活体大脑中突触前多巴胺活性进行定量成像。
