Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats

Fumitaka Ito, Hiroshi Toyama, Gen Kudo, Hiromi Suzuki, Kentaro Hatano, Masanori Ichise, Kazuhiro Katada, Kengo Ito, Makoto Sawada

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective The transition of microglia from the normal resting state to the activated state is associated with an increased expression of peripheral benzodiazepine receptors (PBR). The extent of PBR expression is dependent on the level of microglial activation. A PBR ligand, [11C]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [11C]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation. Methods On day 1, a small aliquot of absolute ethanol was injected into the rat right striatum (ST) to produce artificial brain injury. On day 3, MRI scans were performed to evaluate and select rats showing a similar degree of brain injury. Then LPS or vehicle was administered intraperitoneally. On day 4, PET scans were performed after a bolus injection of [11C]PK11195. Eleven rats (7 LPS administered rats, 4 LPS non-administered rats) were evaluated. We used uptake ratios of the integral of right and left striatum from 0 to 60 min as an estimate of PBR distribution volume (V60). The number of activated microglia and mRNA expression of inflammatory cytokines (TNFα, IL-1β) were assessed by isolectin-B4 staining and RT-PCR, respectively. Results Right/left ST V60 ratios of LPS group were significantly higher than those of non-LPS group (P<0.03). Although there were no significant differences in the number of activated microglia between the two groups, LPS group showed higher expression of inflammatory cytokines (TNFα, IL-1β) than the non-treated group indicating that further activation was induced by LPS treatment. Conclusion The results suggest that intensity of PBR signals in [11C]PK11195 PET may be related to the level of microglial activation rather than the number in activated microglia at least in an artificial brain injury model.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalAnnals of Nuclear Medicine
Volume24
Issue number3
DOIs
Publication statusPublished - 01-04-2010

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Microglia
GABA-A Receptors
Lipopolysaccharides
Brain Injuries
Interleukin-1
Cytokines
Encephalitis
(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
Lectins
Positron-Emission Tomography
Ethanol
Therapeutics
Magnetic Resonance Imaging
Staining and Labeling
Ligands
Polymerase Chain Reaction
Messenger RNA
Injections
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Ito, Fumitaka ; Toyama, Hiroshi ; Kudo, Gen ; Suzuki, Hiromi ; Hatano, Kentaro ; Ichise, Masanori ; Katada, Kazuhiro ; Ito, Kengo ; Sawada, Makoto. / Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats. In: Annals of Nuclear Medicine. 2010 ; Vol. 24, No. 3. pp. 163-169.
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Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats. / Ito, Fumitaka; Toyama, Hiroshi; Kudo, Gen; Suzuki, Hiromi; Hatano, Kentaro; Ichise, Masanori; Katada, Kazuhiro; Ito, Kengo; Sawada, Makoto.

In: Annals of Nuclear Medicine, Vol. 24, No. 3, 01.04.2010, p. 163-169.

Research output: Contribution to journalArticle

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T1 - Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats

AU - Ito, Fumitaka

AU - Toyama, Hiroshi

AU - Kudo, Gen

AU - Suzuki, Hiromi

AU - Hatano, Kentaro

AU - Ichise, Masanori

AU - Katada, Kazuhiro

AU - Ito, Kengo

AU - Sawada, Makoto

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Objective The transition of microglia from the normal resting state to the activated state is associated with an increased expression of peripheral benzodiazepine receptors (PBR). The extent of PBR expression is dependent on the level of microglial activation. A PBR ligand, [11C]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [11C]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation. Methods On day 1, a small aliquot of absolute ethanol was injected into the rat right striatum (ST) to produce artificial brain injury. On day 3, MRI scans were performed to evaluate and select rats showing a similar degree of brain injury. Then LPS or vehicle was administered intraperitoneally. On day 4, PET scans were performed after a bolus injection of [11C]PK11195. Eleven rats (7 LPS administered rats, 4 LPS non-administered rats) were evaluated. We used uptake ratios of the integral of right and left striatum from 0 to 60 min as an estimate of PBR distribution volume (V60). The number of activated microglia and mRNA expression of inflammatory cytokines (TNFα, IL-1β) were assessed by isolectin-B4 staining and RT-PCR, respectively. Results Right/left ST V60 ratios of LPS group were significantly higher than those of non-LPS group (P<0.03). Although there were no significant differences in the number of activated microglia between the two groups, LPS group showed higher expression of inflammatory cytokines (TNFα, IL-1β) than the non-treated group indicating that further activation was induced by LPS treatment. Conclusion The results suggest that intensity of PBR signals in [11C]PK11195 PET may be related to the level of microglial activation rather than the number in activated microglia at least in an artificial brain injury model.

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