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Methods Enzymol. 2014;547:417-31. doi: 10.1016/B978-0-12-801415-8.00020-5.

The use of ¹⁸F-BCPP-EF as a PET probe for complex I activity in the brain.

Author information

1
Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita, Shizuoka, Japan. Electronic address: tsukada@crl.hpk.co.jp.

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.

KEYWORDS:

Aging; Brain; Ischemia; Mitochondria; PET; Parkinson

[Indexed for MEDLINE]

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