%0 Journal Article %J Brain %D 2011 %T 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease. %A Fodero-Tavoletti, Michelle T %A Okamura, Nobuyuki %A Furumoto, Shozo %A Mulligan, Rachel S %A Connor, Andrea R %A McLean, Catriona A %A Cao, Diana %A Rigopoulos, Angela %A Cartwright, Glenn A %A O'Keefe, Graeme %A Gong, Sylvia %A Adlard, Paul A %A Barnham, Kevin J %A Rowe, Christopher C %A Masters, Colin L %A Kudo, Yukitsuka %A Cappai, Roberto %A Yanai, Kazuhiko %A Villemagne, Victor L %K Alzheimer Disease %K Analysis of Variance %K Aniline Compounds %K Animals %K Autoradiography %K Binding Sites %K Brain %K Female %K Fluorodeoxyglucose F18 %K Humans %K Immunohistochemistry %K Male %K Mice %K Quinolines %K Radiopharmaceuticals %K tau Proteins %X

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.

%B Brain %V 134 %P 1089-100 %8 2011 Apr %G eng %N Pt 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/21436112?dopt=Abstract %R 10.1093/brain/awr038