In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease
In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease
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DOI：
10.1111/j.1365-2125.2007.03063.x
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
--
作者：
Okamura, Nobuyuki;Funaki, Yoshihito;Yanai, Kazuhiko
目的观察多奈哌齐与脑内乙酰胆碱酯酶（AChE）的体内结合情况，并建立一种测定口服多奈哌齐结合量的方法。方法将[5-C-11-甲氧基]-多奈哌齐（[C-11]-donepezil）作为正电子发射断层扫描（PET）示踪剂进行放射性标记。用正电子发射计算机断层显像（PET）测定了10例AD患者和6例正常老年人体内[C-11]-多奈哌齐的生物分布。两个AD患者进行额外的PET测量后，口服给药的多奈哌齐6 months.RESULTS[C-11]-多奈哌齐-PET图像显示高密度的示踪剂分布在AChE丰富的大脑区域，如纹状体，丘脑和小脑。与老年正常受试者相比，轻度AD患者在新皮层和海马中表现出约18-20%的多奈哌齐结合减少，而中度AD患者在整个脑中表现出约24-30%的多奈哌齐结合减少。口服多奈哌齐（5 mg/天（-1））诱导AD脑中多奈哌齐结合减少61.6-63.3%。[C-11]-多奈哌齐在海马中的分布体积与AD patients.CONCLUSIONS MMSE评分显著相关，[C-11]-多奈哌齐-PET能够定量测量多奈哌齐在脑中的结合。AD患者表现出脑中多奈哌齐结合的减少，即使在疾病的早期阶段。通过这种技术的纵向评价能够确定口服多奈哌齐的AChE结合占有率。
AIMSThe aims of this study were to visualize in vivo binding of donepezil to acetylcholinesterase (AChE) in the brain and to establish a method for measuring the amount of binding of orally administered donepezil.METHODS[5-C-11-methoxy]-donepezil ([C-11]-donepezil) was radiolabelled as a positron emission tomography (PET) tracer. The biodistribution of [C-11]-donepezil was measured by PET in 10 AD patients and six elderly normal subjects. Two AD patients underwent additional PET measurements after oral administration of donepezil for 6 months.RESULTS[C-11]-donepezil-PET images demonstrated high densities of tracer distribution in AChE-rich brain regions such as the striatum, thalamus, and cerebellum. Compared with elderly normal subjects, patients with mild AD exhibited about 18-20% reduction of donepezil binding in the neocortex and hippocampus, while patients with moderate AD exhibited about 24-30% reduction of donepezil binding throughout the brain. Orally administered donepezil (5 mg day(-1)) induced 61.6-63.3% reduction of donepezil binding in AD brains. The distribution volume of [C-11]-donepezil in the hippocampus was significantly correlated with MMSE scores in AD patients.CONCLUSIONS[C-11]-donepezil-PET enables quantitative measurement of donepezil binding in the brain. AD patients exhibited reduction of donepezil binding in the brain, even in the early stage of disease. Longitudinal evaluation by this technique enables determination of AChE binding occupancy of orally administered donepezil.