18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study

Ann Neurol. 2017 Oct;82(4):622-634. doi: 10.1002/ana.25060.

Abstract

Objective: 18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18 F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).

Methods: Participants underwent magnetic resonance imaging and positron emission tomography for amyloid-β (11 C-PiB or 18 F-florbetapir) and tau (18 F-flortaucipir). 18 F-flortaucipir standardized uptake value ratios were calculated (t = 80-100 minutes, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with receiver operating characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in 1 patient who died 9 months after 18 F-flortaucipir.

Results: Clinical PSP patients showed bilaterally elevated 18 F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain, and dentate nucleus relative to controls and PD patients (voxelwise p < 0.05 family wise error corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (area under the curve [AUC] = 0.872 vs controls, AUC = 0.893 vs PD). PSP clinical severity did not correlate with 18 F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau pathology in PSP-related brain structures with good correspondence between in vivo 18 F-flortaucipir and postmortem tau neuropathology.

Interpretation: 18 F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. Ann Neurol 2017;82:622-634.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aniline Compounds / pharmacokinetics
  • Brain / diagnostic imaging*
  • Brain Mapping
  • Carbolines / pharmacokinetics*
  • Case-Control Studies
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Diagnosis
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / complications
  • Parkinson Disease / diagnostic imaging*
  • Positron-Emission Tomography*
  • Severity of Illness Index
  • Supranuclear Palsy, Progressive / complications
  • Supranuclear Palsy, Progressive / diagnostic imaging*
  • Thiazoles / pharmacokinetics
  • tau Proteins / metabolism*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Carbolines
  • Thiazoles
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole