Hideo Tsukada

By Hideo Tsukada

This chapter discusses the capabilities of positron emission tomography (PET) imaging for the diagnosis of Alzheimer’s disease (AD) with deposition of amyloid-β (Aβ). We conducted a PET scan using 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF), a novel PET probe for mitochondrial complex I (MC-I) activity, in young and aged monkeys to demonstrate the normal aging effects on MC-I activity in the brain. The results revealed an age-related impairment of MC-I activity in the brain. Then, we conducted PET scan using 11C-PIB to detect the Aβ deposition in the some parts, not all, of the brains of some part of aged monkeys. For further assessments, PET scans using 11C-PIB for Aβ, 11C-DPA-713 for inflammation, 18F-fluoro-2-deoxy-D-glucose (18F-FDG) for regional cerebral metabolic rate of glucose (rCMRglc), and 18F-BCPP-EF for MC-I were performed in aged animals. When 18F-BCPP-EF uptake is plotted against 11C-PIB uptake in the cerebral cortical regions, it showed a significant negative correlation between them. Plotting of 11C-DPA-713 uptake against 11C-PIB resulted in a significant positive correlation. In contrast, plotting of rCMRglc against 11C-PIB did not reach a statistically significant level. Taken together, these results strongly suggested that 18F-BCPP-EF could discriminate the neuronally damaged areas with neuroinflammation where 18F-FDG could not, owing to its high uptake into the activated microglia.

Part of the book: Exploring New Findings on Amyloidosis

By Hideo Tsukada

In the last two and half decades, we have conducted research on brain functional imaging in nonhuman primates using animal positron emission tomography (PET) scanners with high spatial resolution. We recently designed and synthesized the novel PET probe [18F]BCPP-EF to quantitatively image mitochondria complex-I (MC-I) activity in the living brain. Brain MC-I activity, measured using [18F]BCPP-EF, was significantly lower in aged monkeys than that in young animals, while no significant reduction was observed in SV2A activity, a synaptic-specific parameter that was measured using [11C]UCB-J. Some aged monkeys exhibited increased amyloid-β deposition in the brain, measured using [11C]PiB, which induced neuroinflammation. A positive correlation was noted with neuroinflammation, measured using [11C]DPA-713 and a negative correlation with MC-I activity. Furthermore, a monkey model of Parkinson’s disease prepared by the chronic administration of MPTP revealed suppressed MC-I activity not only in the nigrostriatal dopamine pathway, measured using [11C]PE2I and [11C]6MemTyr, but also in cortical serotonergic neurons, measured using [11C]DASB. This review introduces the translational application of a novel PET probe for noninvasive MC-I imaging from preclinical to clinical PET measurements.

Part of the book: Mitochondria and Brain Disorders