PET Imaging of Mitochondrial Function in the Living Brain

Abstract

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 [ 18 F]BCPP-EF to quantitatively image mitochondria complex-I (MC-I) activity in the living brain. Brain MC-I activity, measured using [ 18 F] 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 [ 11 C]UCB-J. Some aged monkeys exhibited increased amyloid-β deposition in the brain, measured using [ 11 C]PiB, which induced neuroinflammation. A positive correlation was noted with neuroinflammation, measured using [ 11 C]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 [ 11 C]PE2I and [ 11 C]6MemTyr, but also in cortical serotonergic neurons, measured using [ 11 C]DASB. This review introduces the translational application of a novel PET probe for noninvasive MC-I imaging from preclinical to clinical PET measurements.

Parp mutations protect from mitochondrial toxicity in Alzheimer’s disease

“…Future studies could probe the effect of genetic mutations in PARP1 and CD38 and the dietary intake of vitamin B on mitochondria in patients. Novel positron emission tomography probes can be used to quantify the function of mitochondrial complex 1 non-invasively [32]. They may be used in combination with fluid biomarkers of mitochondrial integrity [33,34].…”