PET imaging of ischemia-induced impairment of mitochondrial compl | 48794

Journal of Neuroscience and Neuropharmacology

PET imaging of ischemia-induced impairment of mitochondrial complex I function in living brain

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Hideo Tsukada

Hamamatsu Photonics K.K., Japan

Scientific Tracks Abstracts: Neurochem Neuropharm

Abstract :

FDG-PET is a well-established technique for quantitative imaging of the regional cerebral metabolic rate of glucose (rCMRglc) in living brain. However, 18F-FDG is taken up into not only normal tissues but also inflammatory regions with microglial activation, which humpers the accurate diagnose of brain function. To solve this problem, the translational research with 18F-BCPP-EF, a novel PET probe for mitochondrial complex 1 (MC-1) activity was conducted using an animal PET in ischemic brains of Cynomolgus monkeys. Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hr, then PET scans were conducted 7 days post ischemic insult with 15O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2), and 18F-BCPP-EF for MC-1, 11C-PBR28 for inflammation (TSPO), and 18F-FDG for rCMRglc. The total distribution volume (VT) values of 18F-BCPP-EF demonstrated the significant reduction of MC-1 activity in the damaged area at Day-7. The VT values of 18F-BCPP-EF provided better correlation with rCMRO2 than rCBF. In the inflammatory regions of the ischemic hemisphere detected with 11C-PBR28, higher 18F-FDG uptake and lower VT of 18F-BCPP-EF, and rCMRO2 than those in normal contralateral hemisphere were observed. Furthermore, the neuroprotective effect of FK506-liposome was detected by 18F-BCPP-EF, as improved MC-I activity, in ischemic-damaged regions. These results strongly suggested that the PET scan using 18F-BCPP-EF could non-invasively diagnose the extent of the brain damage and evaluate the neuroprotective effects without any disturbances by neuroinflammation, where 18F-FDG could not, owing to its high uptake into the activated microglia.

Biography :

Hideo Tsukada received PhD from Shizuoka College of Pharmacy, Japan. He was a Visiting Researcher in Uppsala University PET Center, directed by Professor Bengt Langstrom, from 1990 to 91. At present, he is the Senior Manager of PET Center, Central Research Laboratory, Hamamatsu Photonics, Japan, and conducting PET researches in preclinical to clinical stages. He has published more than 250 papers, being awarded by the Society for Nuclear Medicine (2009), and Japan Molecular Imaging Award (2010). He is serving as the visiting Professor in Hamamatsu University School of Medicine, and University of Shizuoka, School of Pharmaceutical Sciences.