摘要
对脑葡萄糖利用率、氟脱氧-D-葡萄糖([18 F] -FDG)和淀粉样蛋白示踪物β淀粉样沉积的正电子发射断层摄影术研究,已经表明能监测阿尔茨海默病特征性病理变化,可用于疾病的诊断。这项技术在转基因动物模型上的临床前研究将大大促进药物发现和进一步的了解疾病过程。然而从临床前研究得到的这些生物标志物成像的结果却高度不一致,造成了研究者们对动物模型是否能够真正复制的AD表型的疑虑。在此研究中,我们用[18 F] -FDG和[18 F]-AV45双转基因TASTPM小鼠进行体内成像(即先前已介绍的高含量的纤维状淀粉样蛋白β的和低脑葡萄糖利用率与离体技术的转基因模型) 。我们的研究结果显示[18F] -AV45(P <0.0001)老年小鼠TASTPM出现了显著区域普遍下降,并保留显著[18F] -FDG摄取(P <0.05)。体内定量淀粉样蛋白β表现出强烈的(Pearson的R = 0.7078),但不显著(p值= 0.1156),与体外暗示对示踪剂灵敏度的一些因素正相关。而就[18F] -FDG而言,voxelwise分析大大增强的检测代谢减退区域。我们进一步证明适度的神经元丧失(丘脑P = 0.0318),可能与所观察到的代谢减退有关。本研究与欧盟第七框架计划(FP7 / 2007-2013)根据本PharmaCog赠款协议no.115009的创新药物倡议一起进行这项研究。
关键词: [18 f]-AV45
Current Alzheimer Research
Title:Quantitative μPET Imaging of Cerebral Glucose Metabolism and Amyloidosis in the TASTPM Double Transgenic Mouse Model of Alzheimer’s Disease
Volume: 12 Issue: 7
Author(s): Ann-Marie Waldron, Leonie Wyffels, Jeroen Verhaeghe, Astrid Bottelbergs, Jill Richardson, Jonathan Kelley and Mark Schmidt, Sigrid Stroobants, Xavier Langlois and Steven Staelens
Affiliation:
关键词: [18 f]-AV45
摘要: Positron emission tomography studies of cerebral glucose utilization and amyloid-β deposition with fluoro-deoxy-D-glucose ([18F]-FDG) and amyloid tracers have shown characteristic pathological changes in Alzheimer’s Disease that can be used for disease diagnosis and monitoring. Application of this technology to preclinical research with transgenic animal models would greatly facilitate drug discovery and further understanding of disease processes. The results from preclinical studies with these imaging biomarkers have however been highly inconsistent, causing doubts over whether animal models can truly replicate an AD-like phenotype. In this study we performed in vivo imaging with [18F]-FDG and [18F]-AV45 in double transgenic TASTPM mice, a transgenic model that been previously demonstrated high levels of fibrillar amyloid-β and decreases in cerebral glucose utilization with ex vivo techniques. Our results show widespread and significant retention of [18F]-AV45 (p < 0.0001) in aged TASTPM mice in addition to significantregional decreases in [18F]-FDG uptake (p < 0.05). In vivo quantification of amyloid-β showed a strong (Pearson’s r = 0.7078), but not significant (p = 0.1156), positive correlation with ex vivo measures suggesting some limitations on tracer sensitivity. In the case of [18F]-FDG, voxelwise analysis greatly enhanced detection of hypometabolic regions. We further evidenced modest neuronal loss (thalamus p = 0.0318) that could underlie the observed hypometabolism. This research was performed in conjunction with the European Community's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under the PharmaCog Grant Agreement no.115009.
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Ann-Marie Waldron, Leonie Wyffels, Jeroen Verhaeghe, Astrid Bottelbergs, Jill Richardson, Jonathan Kelley and Mark Schmidt, Sigrid Stroobants, Xavier Langlois and Steven Staelens , Quantitative μPET Imaging of Cerebral Glucose Metabolism and Amyloidosis in the TASTPM Double Transgenic Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (7) . https://dx.doi.org/10.2174/1567205012666150710104713
DOI https://dx.doi.org/10.2174/1567205012666150710104713 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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