Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 34, Issue 4, Pages 708-714Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2014.5
Keywords
brain imaging; ischemia; mitochondria; microglia; molecular imaging
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To assess the capability of F-18-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (F-18-BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a specific marker of ischemia-induced neuronal death without being disturbed by inflammation, translational research was conducted using an animal PET in ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hours, then PET scans were conducted at Day-7 with O-15-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolism of oxygen (rCMRO(2)), and F-18-BCPP-EF for MC-I with arterial blood sampling. On Day-8, the additional PET scans conducted with C-11-flumazenil (C-11-FMZ) for central-type benzodiazepine receptors, C-11-PBR28 for translocator protein, and F-18-fluoro-2-deoxy-D-glucose (F-18-FDG) for regional cerebral metabolic rate of glucose (rCMRgIc). The total distribution volume (V-T) values of F-18-BCPP-EF showed the significant reduction in MC-I activity in the damaged area at Day-7. When correlated with rCBF and rCMRO(2), the V-T values of F-18-BCPP-EF provided better correlation with rCMRO(2) than with rCBF. In the inflammatory regions (region of interest, ROIPBR) of the ischemic hemisphere detected with C-11-PBR28, higher F-18-FDG uptake and lower V-T of F-18-BCPP-EF, C-11-FMZ, and rCMRO(2) than those in normal contralateral hemisphere were observed. These results strongly suggested that F-18-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where F-18-FDG could not owing to its high uptake into the activated microglia.
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