18F-Labeled Phenyldiazenyl Benzothiazole for in Vivo Imaging of Neurofibrillary Tangles in Alzheimer's Disease Brains

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• 作者：Kenji Matsumura ; Masahiro Ono ; Hiroyuki Kimura ; Masashi Ueda ; Yuji Nakamoto ; Kaori Togashi ; Yoko Okamoto ; Masafumi Ihara ; Ryosuke Takahashi ; Hideo Saji
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：January 12, 2012
• 年：2012
• 卷：3
• 期：1
• 页码：58-62
• 全文大小：303K
• 年卷期：v.3,no.1(January 12, 2012)
• ISSN：1948-5875

文摘

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 A尾_1鈥?2 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 A尾_1鈥?2 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 A尾_1鈥?2 aggregates). Furthermore, [¹⁸F]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [¹⁸F]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.

Keywords:

Alzheimer's disease (AD); neurofibrillary tangles (NFTs); imaging; benzothiazole; PET