| Budget Amount *help |
¥30,940,000 (Direct Cost: ¥23,800,000、Indirect Cost: ¥7,140,000)
Fiscal Year 2011: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2010: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2009: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
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| Research Abstract |
While considerable effort has focused on developing positron emission tomography β-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 ^<18>F-THK523 as a novel tau imaging radiotracer. In vitro binding studies demonstrated that ^<18>F-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau compared with β-amyloid 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 β-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of ^<18>F-THK523 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 ^<18>F-THK523 fulfils ligand criteria for human imaging trials.
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