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- Title
18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease.
- Authors
Fodero-Tavoletti, Michelle T.; Okamura, Nobuyuki; Furumoto, Shozo; Mulligan, Rachel S.; Connor, Andrea R.; McLean, Catriona A.; Cao, Diana; Rigopoulos, Angela; Cartwright, Glenn A.; O’Keefe, Graeme; Gong, Sylvia; Adlard, Paul A.; Barnham, Kevin J.; Rowe, Christopher C.; Masters, Colin L.; Kudo, Yukitsuka; Cappai, Roberto; Yanai, Kazuhiko; Villemagne, Victor L.
- 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 18F-THK523 as a novel tau imaging radiotracer. In vitro binding studies demonstrated that 18F-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau (K18Δ280K) compared with β-amyloid1–42 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 β-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of 18F-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 18F-THK523 fulfils ligand criteria for human imaging trials.
- Subjects
ANIMAL models of Alzheimer's disease; ANIMAL models of dementia; POSITRON emission tomography; RADIOACTIVE tracers in biology; MEDICAL imaging systems; BINDING sites; TRANSGENIC mice; LABORATORY mice
- Publication
Brain: A Journal of Neurology, 2011, Vol 134, Issue 4, p1089
- ISSN
0006-8950
- Publication type
Article
- DOI
10.1093/brain/awr038