Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology

Arch Neurol. 2011 Nov;68(11):1398-403. doi: 10.1001/archneurol.2011.153. Epub 2011 Jul 11.


Objective: To determine the correspondence of in vivo quantitative estimates of brain uptake of fluorine 18-labeled flutemetamol with immunohistochemical estimates of amyloid levels in patients who underwent previous biopsy.

Design: Cross-sectional study of ¹⁸F-flutemetamol positron emission tomography (PET) findings in patients with prior cortical biopsy specimen stained for the presence or absence of amyloid plaques.

Setting: University hospital. Patients Seven patients who previously had a prior right frontal cortical biopsy at the site of ventriculoperitoneal placement for presumed normal pressure hydrocephalus were recruited. Inclusion criteria included an adequate biopsy specimen for detection and quantification of β-amyloid pathology and age older than 50 years. Intervention All patients underwent an ¹⁸F-flutemetamol PET scan.

Main outcome measures: Quantitative measures of ¹⁸F-flutemetamol uptake (standardized uptake value ratio, a ratio of mean target cortex activity divided by that in a cerebellar reference region) were made at a location contralateral to the biopsy site and compared with estimates of amyloid load based on immunohistochemical and histological staining.

Results: There was complete agreement between visual reads of ¹⁸F-flutemetamol PET scans (3 blinded readers with majority rule) and histology. A regression model, including time from biopsy as a covariate, demonstrated a significant relationship (P = .01) between ¹⁸F-flutemetamol uptake and percentage of area of amyloid measured by a monoclonal antibody raised against amyloid (NAB228). Similar results were found with the amyloid-specific monoclonal antibody 4G8 and Thioflavin S.

Conclusion: To our knowledge, these data are the first to demonstrate the concordance of ¹⁸F-flutemetamol PET imaging with histopathology, supporting its sensitivity to detect amyloid and potential use in the study and detection of Alzheimer disease.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aniline Compounds
  • Benzothiazoles*
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / pathology*
  • Cross-Sectional Studies
  • Female
  • Fluorine Radioisotopes*
  • Humans
  • Male
  • Middle Aged
  • Plaque, Amyloid / diagnostic imaging*
  • Plaque, Amyloid / pathology*
  • Positron-Emission Tomography* / methods
  • Thiazoles


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Benzothiazoles
  • Fluorine Radioisotopes
  • Thiazoles