Imaging mitochondrial complex I activation during a vibrotactile stimulation: A PET study using [18F]BCPP-EF in the conscious monkey brain

J Cereb Blood Flow Metab. 2020 Dec;40(12):2521-2532. doi: 10.1177/0271678X19900034. Epub 2020 Jan 16.

Abstract

In order to evaluate the capability of 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, to assess neuronal activation, an activation PET study was conducted in the conscious monkey brain with a continuous unilateral vibrotactile stimulation. PET scans with [15O]H2O, [18F]BCPP-EF, or 2-deoxy-2-[18F]fluoroglucose ([18F]FDG) were conducted under: (1) resting conditions; (2) a continuous vibration stimulation; (3) a continuous vibration stimulation after 15-min pre-vibration; and (4) a continuous vibration stimulation after 30-min pre-vibration. The contralateral/ipsilateral ratio (CIR) in the somatosensory cortex showed significant increases in the uptake of [15O]H2O, [18F]BCPP-EF, and [18F]FDG with the vibration stimulation. The longer pre-vibration duration induced significantly lower CIR in regional cerebral blood flow (rCBF) measured using [15O]H2O, whereas it did not affect the CIR in [18F]BCPP-EF or the regional cerebral metabolic rate of glucose (rCMRglc) measured using [18F]FDG 30-60 min after the injection. These results suggest that the [18F]BCPP-EF response in the later phase of scans was not influenced by the increase in rCBF, indicating the capability of [18F]BCPP-EF to detect acute changes in MC-I activity induced by neuronal activation. However, the metabolic shift from glycolysis to oxidation was not observed under the stimulation used here.

Keywords: Glycolysis; mitochondrial complex I; monkey brain; neuronal activation; regional cerebral blood flow.

Publication types

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

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Cerebrovascular Circulation / physiology
  • Electron Transport Complex I / metabolism*
  • Fluorodeoxyglucose F18 / metabolism*
  • Glycolysis / physiology
  • Haplorhini / metabolism*
  • Male
  • Neurons / metabolism
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / metabolism
  • Somatosensory Cortex / metabolism
  • Vibration / adverse effects*

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Electron Transport Complex I