18F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains

Kenji Matsumura, Masahiro Ono, Hiroyuki Kimura, Masashi Ueda, Yuji Nakamoto, Kaori Togashi, Yoko Okamoto, Masafumi Ihara, Ryosuke Takahashi, Hideo Saji

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 Aβ 1-42 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 Aβ 1-42 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 Aβ 1-42 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.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number1
DOIs
Publication statusPublished - Jan 12 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Matsumura, K., Ono, M., Kimura, H., Ueda, M., Nakamoto, Y., Togashi, K., Okamoto, Y., Ihara, M., Takahashi, R., & Saji, H. (2012). 18F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains. ACS Medicinal Chemistry Letters, 3(1), 58-62. https://doi.org/10.1021/ml200230e