期刊
BRAIN
卷 134, 期 -, 页码 1089-1100出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awr038
关键词
tau; imaging; Alzheimer's disease; dementia; PET
资金
- National Health and Medical Research Council of Australia
- Neurosciences Victoria
- New Energy and Industrial Technology Development Organization (NEDO) of Japan
- AAR
- NHMRC
- Perpetual Trustees H L Hecht Trust
- Ministry of Health, Labour and Welfare, Japan
- Grants-in-Aid for Scientific Research [23390297] Funding Source: KAKEN
While considerable effort has focused on developing positron emission tomography beta-amyloid imaging radiotracers for the early diagnosis of Alzheimer's disease, no radiotracer is available for the non-invasive quantification of tau. In this study, we detail the characterization of F-18-THK523 as a novel tau imaging radiotracer. In vitro binding studies demonstrated that F-18-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau (K18 delta 280K) compared with beta-amyloid(1-42) fibrils. Autoradiographic and histofluorescence analysis of human hippocampal serial sections with Alzheimer's disease exhibited positive THK523 binding that co-localized with immunoreactive tau pathology, but failed to highlight beta-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of F-18-THK523 (48%; P < 0.007) in tau transgenic mice brains compared with their wild-type littermates or APP/PS1 mice. The preclinical examination of THK523 has demonstrated its high affinity and selectivity for tau pathology both in vitro and in vivo, indicating that F-18-THK523 fulfils ligand criteria for human imaging trials.
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