18F-THK523: A novel in vivo tau imaging ligand for Alzheimer's disease Academic Article uri icon

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

  • Fodero-Tavoletti, MT
  • Okamura, N
  • Furumoto, S
  • Mulligan, RS
  • Connor, AR
  • McLean, CA
  • Cao, D
  • Rigopoulos, A
  • Cartwright, GA
  • O'Keefe, G
  • Gong, S
  • Adlard, PA
  • Barnham, KJ
  • Rowe, CC
  • Masters, CL
  • Kudo, Y
  • Cappai, R
  • Yanai, K
  • Villemagne, VL

publication date

  • 2011