In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand:: [11C]PK-11195 and animal PET following ethanol injury in rat striatum
In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand:: [11C]PK-11195 and animal PET following ethanol injury in rat striatum
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DOI：
10.1007/s12149-008-0136-1
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发表时间：
2008-06-01
影响因子：
2.6
通讯作者：
Ito, Kengo
中科院分区：
文献类型：
--
作者：
Toyama, Hiroshi;Hatano, Kentaro;Ito, Kengo
目的探讨外周苯二氮卓受体（PBRs）特异性配体[（11）C]PK-11195能否在大鼠脑损伤模型中显示活化的小胶质细胞。在第3天，对手术治疗的大鼠进行头部磁共振成像（MRI）扫描，以从形态学上评估乙醇损伤。第4天，在水合氯醛麻醉下，通过尾静脉推注[（11）C]PK-11195后，使用动物PET扫描仪进行动态PET扫描（17只损伤大鼠和7只未损伤对照）60 min。由于PBRs存在于整个大脑中，因此没有合适的无受体参考区域。参考组织模型可能不适用，因为[（11）C]PK-11195对PBRs的亲和力较低，目标与背景比值较低。我们评估了PBRs与基于感兴趣区域（ROI）的方法的结合，以估计总分布体积（V）。我们使用0 min至60 min的积分（V（60））作为V的估计值。在冠状PET图像上，将ROI放置在双侧ST上。使用非配对t检验比较损伤和未损伤对照大鼠之间右/左ST V（60）比值的差异。结果损伤组大鼠左/右ST V（60）比值（1.07 ± 0.08）显著高于对照组（1.00 ± 0.06，P < 0.05）;在免疫组化染色中，只观察到小胶质细胞的激活，而不是在未受伤的左ST的损伤大鼠和未受伤的对照rat.Conclusions这些结果表明，[（11）C]PK-11195 PET成像将是一个有用的工具，用于评估小胶质细胞的激活在大鼠脑损伤模型。
Objective To investigate whether [(11)C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model.Methods On day 1, ethanol was injected into the rat's right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [(11)C]PK-11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to background ratio for low affinity of [(11)C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume (V). We used an integral from 0 min to 60 min (V (60)) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V (60) ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day.Results The right/left ST V (60) ratios in lesioned rats (1.07 +/- 0.08) were significantly higher than those in unlesioned control rats (1.00 +/- 0.06, P < 0.05). On immunohistochemical staining, activated microglia were exclusively observed in the injured right ST but not in the noninjured left ST of the injury rats and the bilateral ST of the non-injured control rats.Conclusions These results suggest that [(11)C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.