Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer's disease.
Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0031310
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Drzezga A
中科院分区：
文献类型：
--
作者：
Manook A;Yousefi BH;Willuweit A;Platzer S;Reder S;Voss A;Huisman M;Settles M;Neff F;Velden J;Schoor M;von der Kammer H;Wester HJ;Schwaiger M;Henriksen G;Drzezga A
阿尔茨海默病（AD）小动物模型中淀粉样蛋白-β斑块（Aβ）负荷的体内成像和定量是转化研究（例如开发特异性成像标记物和监测新治疗方法）的有价值的工具。方法学上的限制，如正电子发射断层扫描（PET）的图像分辨率和缺乏合适的AD模型，限制了PET在小鼠中的可行性。在这项研究中，我们评估了一种可行的方案，用于在小鼠大脑中使用[11 C]PiB和人体研究中常用的特定活性进行Aβ PET成像。使用临床1.5 T系统采集用于解剖参考的体内小鼠脑MRI。最近表征的APP/PS1小鼠用于测量纯合子和半合子动物在不同疾病阶段的Aβ。我们用离体和体外方法对PET结果进行了多模式交叉验证，包括局部脑生物分布、多标记数字放射自显影、ELISA蛋白定量、荧光显微镜、半自动组织学定量和放射性配体结合测定。在研究队列的所有动物（包括9个月大的纯合子AD动物）中，证明并验证了Aβ沉积的单个脑区域中的特异性[11 C]PiB摄取。与Aβ病理学程度相对应，老年纯合子AD动物（21个月）的摄取最高，其次是老年半合子小鼠（23个月）和年轻纯合子小鼠（9个月）。在所有AD年龄组中，小脑被证明适合作为脑内参考区域。PET结果经过交叉验证，与所有应用的离体和体外方法一致。结果证实，APP/PS1小鼠中Aβ非侵入性[11 C]PiB成像的实验装置为小动物Aβ成像提供了可行、可重复和稳健的方案。它允许纵向成像研究，随访期约为一年半，并为转基因小鼠的翻译阿尔茨海默氏症神经成像提供了基础。
In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
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影响因子：
46.9
作者：
Hintersteiner, M;Enz, A;Gremlich, HU
通讯作者：
Gremlich, HU
影响因子：
82.9
作者：
Holcomb, L;Gordon, MN;Duff, K
通讯作者：
Duff, K
影响因子：
4.2
作者：
Dhenain, Marc;El Tayara, Nadine El Tannir;Delatour, Benoit
通讯作者：
Delatour, Benoit
影响因子：
3.5
作者：
Kemp BJ;Hruska CB;McFarland AR;Lenox MW;Lowe VJ
通讯作者：
Lowe VJ
DOI：
10.1016/j.jalz.2011.03.004
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Jack CR Jr;Albert MS;Knopman DS;McKhann GM;Sperling RA;Carrillo MC;Thies B;Phelps CH
通讯作者：
Phelps CH