title: 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease.
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 (K18Δ280K) compared with β-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 β-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of (18)F-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 (18)F-THK523 fulfils ligand criteria for human imaging trials.
authors: Department of Pathology, The University of Melbourne, Victoria, 3010, Australia.
authors: Michelle T
authors: MT
authors: Fodero-Tavoletti
authors: Nobuyuki
authors: N
authors: Okamura
authors: Shozo
authors: S
authors: Furumoto
authors: Rachel S
authors: RS
authors: Mulligan
authors: Andrea R
authors: AR
authors: Connor
authors: Catriona A
authors: CA
authors: McLean
authors: Diana
authors: D
authors: Cao
authors: Angela
authors: A
authors: Rigopoulos
authors: Glenn A
authors: GA
authors: Cartwright
authors: Graeme
authors: G
authors: O'Keefe
authors: Sylvia
authors: S
authors: Gong
authors: Paul A
authors: PA
authors: Adlard
authors: Kevin J
authors: KJ
authors: Barnham
authors: Christopher C
authors: CC
authors: Rowe
authors: Colin L
authors: CL
authors: Masters
authors: Yukitsuka
authors: Y
authors: Kudo
authors: Roberto
authors: R
authors: Cappai
authors: Kazuhiko
authors: K
authors: Yanai
authors: Victor L
authors: VL
authors: Villemagne
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011804:Quinolines / Q000494:pharmacology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C559040:2-(4-aminophenyl)-6-(2-fluoroethoxy)quinoline; D000814:Aniline Compounds; D011804:Quinolines; D019275:Radiopharmaceuticals; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18