Tsukada Hideo, Kanazawa Masakatsu, Ohba Hiroyuki, Nishiyama Shingo, Harada Norihiro, Kakiuchi Takeharu
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan.
J Nucl Med. 2016 Jun;57(6):950-3. doi: 10.2967/jnumed.115.169615. Epub 2016 Feb 11.
(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.
(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.
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.
(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.
使用（18）F-BCPP-EF评估由1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）制备的帕金森病模型猴脑内的线粒体复合体I（MC-I）活性以及突触前多巴胺参数。
静脉注射用于多巴胺转运体的（11）C-β-CFT；用于多巴胺合成的（11）C-3,4-二羟基苯丙氨酸（β-（11）C-L-DOPA）、L-6-（18）F-氟多巴（（18）F-FDOPA）或6-（11）C-甲基-m-酪氨酸（（11）C-6MemTyr）；或用于MC-I的2-叔丁基-4-氯-5-{6-[2-（2-（18）F-氟乙氧基）-乙氧基]-吡啶-3-基甲氧基}-2H-哒嗪-3-酮（（18）F-BCPP-EF）到正常和MPTP处理的猴子体内，以分析它们在纹状体中的摄取情况。
在MPTP处理的猴子纹状体中检测到突触前多巴胺参数和MC-I活性显著降低。在纹状体中观察到MC-I活性与多巴胺转运体之间以及MC-I活性与多巴胺合成之间存在相关性。检测受损MC-I活性的可检测性顺序为（11）C-6MemTyr >> β-（11）C-L-DOPA > （18）F-FDOPA。
（18）F-BCPP-EF有潜力作为一种PET探针，用于使用PET对帕金森病模型猴活体脑内MC-I损伤进行定量成像。
