title: The use of ¹⁸F-BCPP-EF as a PET probe for complex I activity in the brain.
abstract: Mitochondria are called "cellular power plants" because they exclusively contain a respiratory electron transfer chain consisting of five components (complexes I-V) to generate most of the ATP required to maintain cellular functions. Mitochondrial complex I (MC-I) is the first and the largest macrocomplex in the pathway for oxidative phosphorylation. We recently synthesized a series of novel PET probes for quantitative imaging of MC-I activity in the living brain. Several in vitro biological evaluations suggested that (18)F-BCPP-EF could be applicable for MC-I assessment in vivo, and the probe has been applied to several animal disease models of stroke, aging, and dementia. The data suggested that (18)F-BCPP-EF could be useful to detect ischemic neuronal damage at the subacute phase, 7 days, after ischemic insult, at which time unexpectedly higher (18)F-FDG uptake was observed in the damaged area than in the contralateral intact area. Our studies with the aged monkeys demonstrated that (18)F-BCPP-EF detected the age-related reduction of MC-I activity in the living monkey brain, and also that the monkeys with higher amyloid-β deposition showed lower MC-I activity. Since PET is a sophisticated medical modality for noninvasive assessment of real-time tissue function by using target-specific radiolabeled probes, the development of novel PET probes for MC-I should be useful for diagnostic, prognostic, and treatment monitoring of diseases related to impaired MC-I function.
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita, Shizuoka, Japan. Electronic address: tsukada@crl.hpk.co.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
mesh_terms: D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D042967:Electron Transport Complex I / Q000032:analysis* / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D008252:Macaca fascicularis; D008297:Male; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011724:Pyridazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000008:administration & dosage; D020521:Stroke / Q000378:metabolism / Q000473:pathology*
chemical_list: C588084:2-tert-butyl-4-chloro-5-(6-(2-(2-fluoroethoxy)ethoxy)pyridin-3-ylmethoxy)-2H-pyridazin-3-one; D016229:Amyloid beta-Peptides; D015335:Molecular Probes; D011724:Pyridazines; D011725:Pyridines; D012402:Rotenone; D042967:Electron Transport Complex I
keywords: Aging; Brain; Ischemia; Mitochondria; PET; Parkinson