Evaluation of [11C]TAZA for Amyloid β Plaque Imaging in Postmortem Human Alzheimer's Disease Brain Region and Whole Body Distribution in Rodent PET/CT
Evaluation of [11C]TAZA for Amyloid β Plaque Imaging in Postmortem Human Alzheimer's Disease Brain Region and Whole Body Distribution in Rodent PET/CT
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DOI：
10.1002/syn.21893
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发表时间：
2016-04-01
期刊：
影响因子：
2.3
通讯作者：
Mukherjee, Jogeshwar
中科院分区：
文献类型：
--
作者：
Pan, Min-Liang;Mukherjee, Meenakshi T.;Mukherjee, Jogeshwar
目的：阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中存在 Aβ 斑块。本研究的目的是评估新型放射性示踪剂 4-[C-11] 甲氨基-4'-N,N-二甲氨基偶氮苯 ([C-11]TAZA) 与死后人脑（AD 和正常对照 (NC)）中 A β 斑块结合的有效性。方法：使用由[C-11]CO2 制备的[C-11]三氟甲磺酸甲酯进行[C-11]TAZA、相关[C-11]Dalene（C-11-甲氨基-4'-二甲氨基苯乙烯基苯）和参考[C-11]PIB 的放射合成，并使用HPLC 进行纯化。在具有[H-3]PIB标记的Aβ斑块的人AD脑匀浆中进行体外结合亲和力。对 AD 和 NC 大脑的海马体进行了三种放射性示踪剂的体外放射自显影研究。在正常大鼠中进行 PET/CT 研究，以研究大脑和全身分布。结果：三种放射性示踪剂的放射化学产率较高（>40%），比活度>37 GBq/mu mol。 TAZA 的亲和力 K-i=0.84 nM，比 PIB 强五倍。 [C-11]TAZA 特异性结合 AD 大脑中灰质与白质比率 > 20 的 A β 斑块。 [C-11]TAZA 被 PIB 取代 (>90%)，表明 [C-11]TAZA 和 [C-11]PIB 具有相似的结合位点。 [C-11]TAZA 在大鼠大脑中表现出缓慢的摄取动力学，全身图像显示在肩胛间棕色脂肪组织 (IBAT) 中的摄取。预先注射去甲肾上腺素转运阻滞剂托莫西汀会影响大脑和 IBAT 的结合。结论：[C-11]TAZA 与人 AD 海马中的 Aβ 斑块表现出高度结合。大鼠大脑动力学缓慢，外周与 IBAT 的结合需要进一步评估。 Synapse (C) 2016 Wiley 期刊公司
Objective: Alzheimer's disease (AD) is a neurodegenerative disease characterized by A beta plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[C-11]methylamino-4'-N,N-dimethylaminoazobenzene ([C-11]TAZA), for binding to A beta plaques in postmortem human brain (AD and normal control (NC)). Methods: Radiosyntheses of [C-11]TAZA, related [C-11]Dalene (C-11-methylamino-4'-dimethylaminostyrylbenzene), and reference [C-11]PIB were carried out using [C-11]methyltriflate prepared from [C-11]CO2 and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with A beta plaques labeled with [H-3]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. Results: The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/mu mol. TAZA had an affinity, K-i=0.84 nM and was five times more potent than PIB. [C-11]TAZA bound specifically to A beta plaques present in AD brains with gray matter to white matter ratios >20. [C-11]TAZA was displaced by PIB (>90%), suggesting similar binding site for [C-11]TAZA and [C-11]PIB. [C-11]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. Conclusion: [C-11]TAZA exhibited high binding to A beta plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. Synapse (C) 2016 Wiley Periodicals, Inc.