Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer's Disease.
Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer's Disease.
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DOI：
10.1038/srep35636
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发表时间：
2016-11-02
影响因子：
4.6
通讯作者：
Sharma V
中科院分区：
文献类型：
--
作者：
Sundaram GS;Dhavale DD;Prior JL;Yan P;Cirrito J;Rath NP;Laforest R;Cairns NJ;Lee JM;Kotzbauer PT;Sharma V
作为一种新型的平面苯并硒(5)，在体内非侵入性成像Aβ病理生理学；标记阿尔茨海默病(AD)脑切片中的弥漫性(神经性斑块的早期表现)和纤维斑块；与其他神经退行性疾病的生物标记物蛋白相比，在定位Aβ方面具有显著的特异性。使用AD匀浆，[18F]-9，PET示踪剂显示出比FDA批准的示踪剂更高的结合亲和力(2-10倍)，同时也表明结合到Aβ斑块上的高亲和力部位。药代动力学研究表明，[18F]-9在正常小鼠脑内的初始高流入伴随着在没有靶向斑块的情况下的快速清除。在人血清中孵育后，[18F]-9表明在3h内有亲本化合物的存在，从而表明其稳定性。此外，[18F]-9与AD脑组织切片的体外放射自显影研究和转基因小鼠脑切片的体外放射自显影研究表明，皮质Aβ结合，并与Aβ免疫染色有良好的相关性。最后，多光子和微型PET/CT成像表明它有能力穿透大脑并标记转基因小鼠的实质斑块。在进一步验证其在其他AD啮齿动物模型和非人灵长类动物中的性能后，Fluselenamyl可以为在体内监测Aβ早期病理生理学提供一种平台技术。
Fluselenamyl (5), a novel planar benzoselenazole shows traits desirable of enabling noninvasive imaging of Aβ pathophysiology in vivo; labeling of both diffuse (an earlier manifestation of neuritic plaques) and fibrillar plaques in Alzheimer’s disease (AD) brain sections, and remarkable specificity for mapping Aβ compared with biomarker proteins of other neurodegenerative diseases. Employing AD homogenates, [18F]-9, a PET tracer demonstrates superior (2–10 fold higher) binding affinity than approved FDA tracers, while also indicating binding to high affinity site on Aβ plaques. Pharmacokinetic studies indicate high initial influx of [18F]-9 in normal mice brains accompanied by rapid clearance in the absence of targeted plaques. Following incubation in human serum, [18F]-9 indicates presence of parental compound up to 3h thus indicating its stability. Furthermore, in vitro autoradiography studies of [18F]-9 with AD brain tissue sections and ex vivo autoradiography studies in transgenic mouse brain sections show cortical Aβ binding, and a fair correlation with Aβ immunostaining. Finally, multiphoton- and microPET/CT imaging indicate its ability to penetrate brain and label parenchymal plaques in transgenic mice. Following further validation of its performance in other AD rodent models and nonhuman primates, Fluselenamyl could offer a platform technology for monitoring earliest stages of Aβ pathophysiology in vivo.
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DOI：
10.1073/pnas.1107411108
发表时间：
2011-09-06
影响因子：
11.1
作者：
Cirrito, John R.;Disabato, Brianne M.;Sheline, Yvette I.
通讯作者：
Sheline, Yvette I.
影响因子：
9.3
作者：
Koole, Michel;Lewis, Dewi M.;Van Laere, Koen
通讯作者：
Van Laere, Koen
影响因子：
11.2
作者：
Klunk, WE;Engler, H;Långström, B
通讯作者：
Långström, B
影响因子：
168.9
作者：
Ferri, CP;Prince, M;Scazufca, M
通讯作者：
Scazufca, M
DOI：
10.1073/pnas.162228299
发表时间：
2002-08-06
影响因子：
11.1
作者：
DeMattos, RB;O'dell, MA;Holtzman, DM
通讯作者：
Holtzman, DM