[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease

Eur J Nucl Med Mol Imaging. 2015 Jun;42(7):1052-61. doi: 10.1007/s00259-015-3035-4. Epub 2015 Mar 20.

Abstract

Purpose: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer.

Methods: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks.

Results: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex.

Conclusion: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology
  • Aniline Compounds / pharmacokinetics*
  • Aniline Compounds / pharmacology
  • Benzothiazoles
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology
  • Female
  • Humans
  • Male
  • Neurofibrils / diagnostic imaging*
  • Neurofibrils / pathology
  • Positron-Emission Tomography*
  • Quinolines / pharmacokinetics*
  • Quinolines / pharmacology
  • Radiopharmaceuticals*
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • 6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline
  • Aniline Compounds
  • Benzothiazoles
  • Quinolines
  • Radiopharmaceuticals
  • THK5105
  • Thiazoles