Comparing amyloid-β deposition, neuroinflammation, glucose metabolism, and mitochondrial complex I activity in brain: a PET study in aged monkeys

Eur J Nucl Med Mol Imaging. 2014 Nov;41(11):2127-36. doi: 10.1007/s00259-014-2821-8. Epub 2014 Jun 12.

Abstract

Purpose: The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys.

Methods: PET scans with (11)C-PIB (Aβ), (18)F-BCPP-EF (MC-I), (11)C-DPA-713 (TSPO), and (18)F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. (11)C-PIB binding to Aβ and (11)C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V T) of (18)F-BCPP-EF and rCMRglc with (18)F-FDG were calculated using arterial blood sampling.

Results: Isoflurane did not affect MC-I activity measured in terms of (18)F-BCPP-EF uptake in living brain. There was a significant negative correlation between (18)F-BCPP-EF binding (V T) and (11)C-PIB uptake (SUVR), and there was a significant positive correlation between (11)C-DPA-713 uptake (SUV) and (11)C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and (11)C-PIB uptake.

Conclusion: (18)F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain.

Publication types

  • Comparative Study

MeSH terms

  • Aging / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Electron Transport Complex I / metabolism*
  • Glucose / metabolism
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Macaca mulatta
  • Male
  • Positron-Emission Tomography*
  • Pyridazines
  • Pyridines

Substances

  • 2-tert-butyl-4-chloro-5-(6-(2-(2-fluoroethoxy)ethoxy)pyridin-3-ylmethoxy)-2H-pyridazin-3-one
  • Amyloid beta-Peptides
  • Pyridazines
  • Pyridines
  • Electron Transport Complex I
  • Glucose