Get access

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

Authors


Abstract

The acute and subacute ischemic neuronal damage in rat brain caused by photochemically induced thrombosis (PIT) was imaged using [18F]BMS-747158-02 ([18F]BMS) for mitochondrial complex-1 (MC-1) and [11C](R)-PK11195 ([11C](R)-PK) for peripheral benzodiazepine receptor [PBR; translocator protein] at preischemic “Normal,” 1 (day 1), and 7 days (day 7) after ischemic insult. When [18F]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 [18F]BMS binding to MC-1 was also confirmed by living brain slice imaging. At day 1, [18F]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 [18F]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 [11C](R)-PK imaging and immunohistochemical assessment with Iba1 antibody. In contrast, the uptake pattern of [18F]BMS was consistent with immunohistochemical assessment with NeuN antibody at both days 1 and 7. These results demonstrated that [18F]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.

Get access to the full text of this article

Ancillary