Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging

Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Yoichi Ishikawa, Hiroyuki Arai, Kazuhiko Yanai, Ren Iwata, Yukitsuka Kudo

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Alzheimer's disease (AD) is the most common cause of dementia. Senile plaques, consisting of β-amyloid, and neurofibrillary tangles (NFTs), composed of tau protein, are representative pathological hallmarks of AD. It is believed that the accumulation of NFTs precedes the onset of clinical symptoms of AD and correlates with the progression of memory dysfunction. Thus, the use of noninvasive detection techniques including radiolabeled probes and positron emission tomography (PET) will facilitate early diagnosis or staging of AD. In this study, we synthesized and evaluated novel hydroxylated 2-arylquinoline derivatives as tau imaging PET probes. The binding affinities of compounds for tau were evaluated by fluorescent staining of the AD hippocampal section and a competitive binding assay using [18F]THK-523. THK-951 showed high binding affinity for tau pathology in an AD brain section and K18Δ280K fibrils (Ki = 20.7 nM); thus, we radiosynthesized a 11C-labeled THK-951 and further studied its potential as a tau PET probe. The [11C]THK-951 demonstrated excellent kinetics in a normal mouse brain (3.23% ID/g at 2 min postinjection and 0.15% ID/g at 30 min postinjection) and showed the labeling of NFTs in an AD brain section by autoradiography assay. These findings indicate the availability of [ 11C]THK-951 for in vivo PET imaging of tau pathology in AD.

Original languageEnglish
Pages (from-to)18-24
Number of pages7
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Issue number1
Publication statusPublished - 2014 Jan


  • Alzheimer's disease
  • imaging
  • positron emission tomography
  • tau


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