[18F]-Flutemetamol Uptake in Cortex and White Matter: Comparison with Cerebrospinal Fluid Biomarkers and [18F]-Fludeoxyglucose

J Alzheimers Dis. 2018;62(4):1595-1607. doi: 10.3233/JAD-170582.

Abstract

Flutemetamol (18F-Flut) is an [18F]-labelled amyloid PET tracer with increasing availability. The main objectives of this study were to investigate 1) cerebrospinal fluid (CSF) Aβ 1-42 (Aβ42) concentrations associated with regional 18F-Flut uptake, 2) associations between cortical 18F-Flut and [18F]-fludeoxyglucose (18F-FDG)-PET, and 3) the potential use of 18F-Flut in WM pathology. Cognitively impaired, nondemented subjects were recruited (n = 44). CSF was drawn, and 18F-Flut-PET, 18F-FDG-PET, and MRI performed. Our main findings were: 1) Different Alzheimer's disease predilection areas showed increased 18F-Flut retention at different CSF Aβ42 concentrations (posterior regions were involved at higher concentrations). 2) There were strong negative correlations between regional cortical 18F-Flut and 18F-FDG uptake. 3) Increased 18F-Flut uptake were observed in multiple subcortical regions in amyloid positive subjects, including investigated reference regions. However, WM hyperintensity 18F-Flut standardized uptake value ratios (SUVr) were not significantly different, thus we cannot definitely conclude that the higher uptake in 18F-Flut(+) is due to amyloid deposition. In conclusion, our findings support clinical use of CSF Aβ42, putatively relate decreasing CSF Aβ42 concentrations to a sequence of regional amyloid deposition, and associate amyloid pathology to cortical hypometabolism. However, we cannot conclude that 18F-Flut-PET is a suitable marker for WM pathology due to high aberrant WM uptake.

Keywords: Alzheimer’s disease; cerebrospinal fluid; imaging; positron emission tomography; white matter disease.

Publication types

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

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Aniline Compounds*
  • Benzothiazoles*
  • Biomarkers / cerebrospinal fluid
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Cognitive Dysfunction / diagnosis*
  • Diagnostic Self Evaluation
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Perception
  • Radiopharmaceuticals*
  • White Matter / diagnostic imaging*
  • White Matter / metabolism

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Biomarkers
  • Peptide Fragments
  • Radiopharmaceuticals
  • amyloid beta-protein (1-42)
  • flutemetamol
  • Fluorodeoxyglucose F18