Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET:: An imaging tool for glial cells in the brain
Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET:: An imaging tool for glial cells in the brain
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DOI：
10.1002/syn.20027
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发表时间：
2004-06-15
期刊：
影响因子：
2.3
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Maeda, J;Suhara, T;Suzuki, K
外周苯二氮卓受体（PBR）在大多数器官中表达，据报道其表达在脑中活化的小胶质细胞中增加。[C-11] PK 11195已广泛用于PBRs的体内成像，但其在脑中的信号不足以进行稳定的定量分析。我们合成了一种新的正电子发射断层扫描（PET）配体，[C-11] DAA 1106，用于PBR，并研究了其在大鼠和猴脑中的体内性质。通过大鼠脑的体内放射自显影，在嗅球和脉络丛区域观察到[C-11] DAA 1106的高摄取，其次是脑桥/延髓和小脑，与体外结合相关。[C-11] DA 1106结合在背侧海马中增加，伴有神经破坏，表明神经胶质反应。1.0 mg/kg DAA 1106和5 mg/kg PK 11195对[C-11] DAA 1106结合的抑制和置换分别为80%和70%。特异性结合估计为总结合的80%。在猴枕叶皮质中，[C-11] DAA 1106的结合是[C-11] PK 11195结合的4倍。这些结果表明，[C-11] DAA 1106可能是一个很好的PBR体内显像的配体。Synapse 52：283-291，2004年。(C)2004 Wiley-Liss，Inc.
Peripheral benzodiazepine receptor (PBR) is expressed in most organs and its expression is reported to be increased in activated microglia in the brain. [C-11] PK11195 has been widely used for the in vivo imaging of PBRs, but its signal in the brain was not high enough for stable quantitative analysis. We synthesized a novel positron emission tomography (PET) ligand, [C-11]DAA1106, for PBR and investigated its in vivo properties in rat and monkey brain. High uptake of [C-11]DAA1106 was observed in the olfactory bulb and choroid plexus area, followed by the pons/medulla and cerebellum by in vivo autoradiography of rat brain, correlating with the binding in vitro. [C-11]DAA1106 binding was increased in the dorsal hippocampus with neural destruction, suggesting glial reaction. [C-11]DAA1106 binding was both inhibited and displaced by 1.0 mg/kg of DAA1106 and 5 mg/kg of PK11195 by 80% and 70%, respectively. Specific binding was estimated as 80% of total binding. [C-11]DAA1106 binding was four times higher compared to the binding of [C-11]PK11195 in the monkey occipital cortex. These results indicated that [C-11]DAA1106 might be a good ligand for in vivo imaging of PBR. Synapse 52:283-291, 2004. (C) 2004 Wiley-Liss, Inc.