(18)F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains.
(18)F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains.
复制标题
DOI：
10.1021/ml200230e
复制
发表时间：
2012-01
影响因子：
4.2
通讯作者：
K. Matsumura;M. Ono;H. Kimura;M. Ueda;Y. Nakamoto;K. Togashi;Y. Okamoto;M. Ihara;R. Takahashi;H. Saji
中科院分区：
文献类型：
--
作者：
K. Matsumura;M. Ono;H. Kimura;M. Ueda;Y. Nakamoto;K. Togashi;Y. Okamoto;M. Ihara;R. Takahashi;H. Saji
我们合成并评估了 (E)-4-((6-(2-(2-(2-氟乙氧基)乙氧基)乙氧基)苯并[d]噻唑-2-基)二氮烯基)-N,N-二甲基苯胺 (FPPDB) 作为阿尔茨海默病 (AD) 患者神经原纤维缠结 (NFT) 成像的探针。在使用硫黄素 S (ThS) 作为竞争性配体的测定中，FPPDB 与 ThS 竞争良好，并对 tau 和 Aβ1-42 聚集体表现出高亲和力（K i 分别为 13.0 和 20.0 nM）。饱和结合测定的结果还验证了 FPPDB 以高亲和力结合 tau 和 Aβ1-42 聚集体（对于 tau 聚集体，K d = 44.8 nM 和 B max = 45.8 pmol/nmol 蛋白质，对于 Aβ1-42 聚集体，K d = 45.4 nM 和 B max = 38.9 pmol/nmol 蛋白质）。此外，[(18)F]FPPDB 显着标记了 AD 脑切片中的 NFT 和老年斑，但未标记对照脑切片。在使用正常小鼠的生物分布实验中，随着时间的推移，[(18)F]FPPDB 显示出较高的大脑摄取量（注射后 2 分钟为 4.28% ID/g）和从大脑中的清除量（注射后 60 分钟为 2.53% ID/g）。基于 FPPDB 的化学结构，进一步增加与 tau 聚集体的选择性结合可能会导致开发出更有用的探针，用于 AD 大脑中 NFT 的成像。
We synthesized and evaluated (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and Aβ1-42 aggregates (K i = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and Aβ1-42 aggregates with high affinity (K d = 44.8 nM and B max = 45.8 pmol/nmol protein for tau aggregates and K d = 45.4 nM and B max = 38.9 pmol/nmol protein for Aβ1-42 aggregates). Furthermore, [(18)F]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [(18)F]FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains.