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

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.