The study for imaging, in vivo, brain mitochondrial. dysfunction using positron emission tomography

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Mounting evidences indicate that the mitochondria play a key role in many diseases of the brain. To analyze mitochondrial function, therefore, provides the important information for diagnosis of the brain diseases. On the other hand, positron emission tomography (PET) is a valuable tool for the study of brain function. However, there is no suitable PET tracer for direct analysis of mitochondrial function. In this study, we employed ^<11>C-pyruvate as a PET tracer, and attempted to analyze mitochondrial function in the brain.A mitochondrial uncoupler, carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP, 10 μM) induced, within 20 min, the impairment of mitochondrial membrane potential in the cultured hippocampal neurons. FCCP significantly decreased ^<11>C-pyruvate radioactivity indicating that ^<11>C-pyruvate may be useful for analyzing mitochondrial function in vitro. We also studied the feasibility of ^<11>C-pyruvate using in vivo rat model of excitotoxicity mediated by intrastriatal injection of 3-nitropropionic acid (3-NP), a succinate dehydrogenase inhibitor. The in vivo study suggests that : 1) ^<11>C-pyruvate can be useful for detecting the mitochondrial dysfunction in the animal model ; and 2) ^<11>C-pyruvate can be used as a PET tracer as follows : a) ^<11>C'-pyruvate intravenously injected ; and b) 10-20 min after injection, PET scan performed and PET mages analyzed. Finally we examined the possibility of ^<11>C-pyruvate using PET scanner following reversible middle cerebral artery occlusion in monkey. ^<11>C-pyruvate showed the similar pattern as indicated by ^<18>F-fluorodeoxyglucose (^<18>F-FDG). Based on these results, we conclude that, as a PET tracer, ^<11>C-pyruvate is valuable to detect the brain mitochondrial dysfunction in vitro and in vivo.