Detection of ischemic neuronal damage with [ 18 F]BMS‐747158‐02, a mitochondrial complex‐1 positron emission tomography ligand: Small animal PET study in rat brain

The acute and subacute ischemic neuronal damage in rat brain caused by photochemically induced thrombosis (PIT) was imaged using [ 18 F]BMS‐747158‐02 ([ 18 F]BMS) for mitochondrial complex‐1 (MC‐1) and [ 11 C](R)‐PK11195 ([ 11 C](R)‐PK) for peripheral benzodiazepine receptor [PBR; translocator protein] at preischemic “Normal,” 1 (day 1), and 7 days (day 7) after ischemic insult. When [ 18 F]BMS was intravenously injected into “Normal” rat, it was rapidly taken up into the brain, in which it showed a homogeneous distribution, and the uptake was suppressed by rotenone, a specific MC‐1 inhibitor. The specificity of [ 18 F]BMS binding to MC‐1 was also confirmed by living brain slice imaging. At day 1, [ 18 F]BMS uptake was low in infarct and peri‐infarct regions where neuronal damage was detected by 2,3,5‐triphenyltetrazolium chloride (TTC) staining. At day 7, the damaged areas determined using [ 18 F]BMS revealed some discrepancy from those detected by TTC staining, suggesting that TTC stained not only surviving cells but also activated microglial cells in the peri‐infarct region. This was also confirmed by [ 11 C](R)‐PK imaging and immunohistochemical assessment with Iba1 antibody. In contrast, the uptake pattern of [ 18 F]BMS was consistent with immunohistochemical assessment with NeuN antibody at both days 1 and 7. These results demonstrated that [ 18 F]BMS could be a promising positron emission tomography ligand to assess the neuronal damage induced by ischemic insult in both acute and subacute phases. Synapse 2012. © 2012 Wiley Periodicals, Inc.