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

Abstract

(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.

PET Imaging of Mitochondrial Complex I with 18F-BCPP-EF in the Brains of MPTP-Treated Monkeys

“…18 F-fluorobenzyl triphenylphosphonium cation was reported to bind to mitochondria, reflecting their membrane potential with voltage-dependency (21); however, this PET probe has not been applied for imaging of mitochondrial function in the living brain. In contrast, our previous reports demonstrated the first PET probe as 18 F-BCPP-EF for MC-I imaging in the living brain (6)(7)(8).…”

“…In addition to dopamine, we recently designed a PET probe, 2-tert-butyl-4-chrolo-5-{6-[2-(2-18 F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ( 18 F-BCPP-EF), for the quantitative imaging of MC-I in vivo and confirmed that it was suitable for imaging MC-I function in the living brains of rats (6) and monkeys (7,8).…”

“…Radiochemical purity was greater than 99%, and specific radioactivity was 40.0 6 10.1 GBq/mmol. 18 F-BCPP-EF was radiolabeled by the nucleophilic 18 F-fluorination of the corresponding precursor (6)(7)(8). Radiochemical purity was greater than 98%, and specific radioactivity was 139.6 6 37.0 GBq/mmol.…”

“…The input function of unmetabolized 18 F-BCPP-EF was calculated using the data obtained by correction of the ratio of the unmetabolized fraction to total radioactivity, which was used as the arterial input function. A kinetic analysis of 18 F-BCPP-EF was performed using the Logan graphical analysis (7,8).…”

Mitochondria and aging: A role for the mitochondrial transition pore?

“…This is particularly true for Alzheimer's disease which is characterized by the presence of extracellular senile plaques, mainly composed of amyloid‐β (Aβ) peptide and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein (Selkoe, 2004). Several studies demonstrate that the Aβ peptide accumulates progressively into mitochondria (Hansson Petersen et al., 2008; Manczak et al., 2006) where it inhibits the activities of the respiratory chain complex and thus oxidative phosphorylation ( Hernandez‐Zimbron et al., 2012; Lahmy, Long, Morin, Villard, & Maurice, 2015; Tillement, Lecanu, & Papadopoulos, 2011; Tsukada et al., 2014). The Aβ peptide can also potentially cause mPTP opening in vivo as it induces mitochondrial swelling, decreases mitochondrial membrane potential, and potentiates the effect of mPTP inducers in isolated brain mitochondria (Du et al., 2008; Moreira, Santos, Moreno, & Oliveira, 2001; Shevtzova, Kireeva, & Bachurin, 2001).…”