Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients

Eur J Neurol. 2013 Jul;20(7):1043-52. doi: 10.1111/ene.12102. Epub 2013 Feb 11.

Abstract

Background and purpose: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.

Methods: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.

Results: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).

Conclusions: [18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds* / adverse effects
  • Benzothiazoles* / adverse effects
  • Biopsy
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Female
  • Functional Neuroimaging
  • Humans
  • Hydrocephalus, Normal Pressure / diagnostic imaging
  • Hydrocephalus, Normal Pressure / metabolism*
  • Hydrocephalus, Normal Pressure / pathology*
  • Male
  • Plaque, Amyloid / pathology
  • Radionuclide Imaging
  • Sensitivity and Specificity
  • Thiazoles*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Thiazoles
  • flutemetamol