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

Hiroshi Toyama, Kentaro Hatano, Hiromi Suzuki, Masanori Ichise, Sotaro Momosaki, Gen Kudo, Fumitaka Ito, Takashi Kato, Hiroshi Yamaguchi, Kazuhiro Katada, Makoto Sawada, Kengo Ito

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 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.

Original languageEnglish
Pages (from-to)417-424
Number of pages8
JournalAnnals of Nuclear Medicine
Volume22
Issue number5
DOIs
Publication statusPublished - 01-06-2008

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GABA-A Receptors
Positron-Emission Tomography
Ethanol
Ligands
Wounds and Injuries
Microglia
Brain Injuries
PK 11195
Staining and Labeling
Chloral Hydrate
Decapitation
Operative Surgical Procedures
Tail
Veins
Anesthesia
Head
Magnetic Resonance Imaging
Injections
Brain

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Toyama, Hiroshi ; Hatano, Kentaro ; Suzuki, Hiromi ; Ichise, Masanori ; Momosaki, Sotaro ; Kudo, Gen ; Ito, Fumitaka ; Kato, Takashi ; Yamaguchi, Hiroshi ; Katada, Kazuhiro ; Sawada, Makoto ; Ito, Kengo. / In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand : [11C]PK-11195 and animal PET following ethanol injury in rat striatum. In: Annals of Nuclear Medicine. 2008 ; Vol. 22, No. 5. pp. 417-424.
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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 (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 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.",
author = "Hiroshi Toyama and Kentaro Hatano and Hiromi Suzuki and Masanori Ichise and Sotaro Momosaki and Gen Kudo and Fumitaka Ito and Takashi Kato and Hiroshi Yamaguchi and Kazuhiro Katada and Makoto Sawada and Kengo Ito",
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Toyama, H, Hatano, K, Suzuki, H, Ichise, M, Momosaki, S, Kudo, G, Ito, F, Kato, T, Yamaguchi, H, Katada, K, Sawada, M & Ito, K 2008, 'In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum', Annals of Nuclear Medicine, vol. 22, no. 5, pp. 417-424. https://doi.org/10.1007/s12149-008-0136-1

In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand : [11C]PK-11195 and animal PET following ethanol injury in rat striatum. / Toyama, Hiroshi; Hatano, Kentaro; Suzuki, Hiromi; Ichise, Masanori; Momosaki, Sotaro; Kudo, Gen; Ito, Fumitaka; Kato, Takashi; Yamaguchi, Hiroshi; Katada, Kazuhiro; Sawada, Makoto; Ito, Kengo.

In: Annals of Nuclear Medicine, Vol. 22, No. 5, 01.06.2008, p. 417-424.

Research output: Contribution to journalArticle

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T1 - In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand

T2 - [11C]PK-11195 and animal PET following ethanol injury in rat striatum

AU - Toyama, Hiroshi

AU - Hatano, Kentaro

AU - Suzuki, Hiromi

AU - Ichise, Masanori

AU - Momosaki, Sotaro

AU - Kudo, Gen

AU - Ito, Fumitaka

AU - Kato, Takashi

AU - Yamaguchi, Hiroshi

AU - Katada, Kazuhiro

AU - Sawada, Makoto

AU - Ito, Kengo

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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 (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 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.

AB - 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 (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 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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