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比较老年猴子大脑中的淀粉样β蛋白沉积、神经炎症、葡萄糖代谢和线粒体复合体I活性:一项PET研究

Comparing amyloid-β deposition, neuroinflammation, glucose metabolism, and mitochondrial complex I activity in brain: a PET study in aged monkeys.

作者信息

Tsukada Hideo, Nishiyama Shingo, Ohba Hiroyuki, Kanazawa Masakatsu, Kakiuchi Takeharu, Harada Norihiro

机构信息

Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Shizuoka, 434-8601, Japan,

出版信息

Eur J Nucl Med Mol Imaging. 2014 Nov;41(11):2127-36. doi: 10.1007/s00259-014-2821-8. Epub 2014 Jun 12.

DOI:10.1007/s00259-014-2821-8
PMID:24919653
Abstract

PURPOSE

The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys.

METHODS

PET scans with (11)C-PIB (Aβ), (18)F-BCPP-EF (MC-I), (11)C-DPA-713 (TSPO), and (18)F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. (11)C-PIB binding to Aβ and (11)C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V T) of (18)F-BCPP-EF and rCMRglc with (18)F-FDG were calculated using arterial blood sampling.

RESULTS

Isoflurane did not affect MC-I activity measured in terms of (18)F-BCPP-EF uptake in living brain. There was a significant negative correlation between (18)F-BCPP-EF binding (V T) and (11)C-PIB uptake (SUVR), and there was a significant positive correlation between (11)C-DPA-713 uptake (SUV) and (11)C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and (11)C-PIB uptake.

CONCLUSION

(18)F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain.

摘要

目的

本研究旨在比较老年猴大脑中β淀粉样蛋白(Aβ)沉积、转位蛋白(TSPO)活性、局部脑葡萄糖代谢率(rCMRglc)和线粒体复合物I(MC-I)活性。

方法

对清醒状态和异氟烷麻醉下的老年恒河猴(猕猴)进行正电子发射断层扫描(PET),分别使用(11)C-PIB(用于检测Aβ)、(18)F-BCPP-EF(用于检测MC-I)、(11)C-DPA-713(用于检测TSPO)和(18)F-FDG(用于检测rCMRglc)。根据标准摄取值(SUV)评估(11)C-PIB与Aβ的结合以及(11)C-DPA-713与TSPO的结合。通过动脉血采样计算(18)F-BCPP-EF的分布总体积(VT)和(18)F-FDG的rCMRglc。

结果

异氟烷不影响活体大脑中通过(18)F-BCPP-EF摄取测量的MC-I活性。(18)F-BCPP-EF结合(VT)与(11)C-PIB摄取(SUVR)之间存在显著负相关,(11)C-DPA-713摄取(SUV)与(11)C-PIB摄取之间存在显著正相关。相比之下,rCMRglc比值与(11)C-PIB摄取之间无显著相关性。

结论

(18)F-BCPP-EF可能是一种潜在的PET探针,用于定量成像与活体大脑中Aβ沉积相关的受损MC-I活性。

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