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In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum

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Abstract

Objective

To investigate whether [11C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model.

Methods

On day 1, ethanol was injected into the rat’s right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [11C]PK-11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to background ratio for low affinity of [11C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume (V). We used an integral from 0 min to 60 min (V 60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V 60 ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day.

Results

The right/left ST V 60 ratios in lesioned rats (1.07 ± 0.08) were significantly higher than those in unlesioned control rats (1.00 ± 0.06, P < 0.05). On immunohistochemical staining, activated microglia were exclusively observed in the injured right ST but not in the noninjured left ST of the injury rats and the bilateral ST of the non-injured control rats.

Conclusions

These results suggest that [11C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.

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Authors and Affiliations

  1. Department of Radiology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan

    Hiroshi Toyama, Gen Kudo, Fumitaka Ito & Kazuhiro Katada

  2. Department of Brain Science and Molecular Imaging, National Institute for Longevity Sciences, Obu, Japan

    Kentaro Hatano, Sotaro Momosaki, Takashi Kato, Hiroshi Yamaguchi & Kengo Ito

  3. Department of Brain Life Science, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan

    Hiromi Suzuki & Makoto Sawada

  4. Department of Radiology, Columbia University, New York, NY, USA

    Masanori Ichise

Authors
  1. Hiroshi Toyama
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  2. Kentaro Hatano
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  3. Hiromi Suzuki
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Correspondence to Hiroshi Toyama.

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Toyama, H., Hatano, K., Suzuki, H. et al. In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum. Ann Nucl Med 22, 417–424 (2008). https://doi.org/10.1007/s12149-008-0136-1

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  • DOI: https://doi.org/10.1007/s12149-008-0136-1

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