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

Objective To investigate whether [ 11 C]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 stereotax...

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Veröffentlicht in:Annals of nuclear medicine 2008-06, Vol.22 (5), p.417-424
Hauptverfasser: Toyama, Hiroshi, Hatano, Kentaro, Suzuki, Hiromi, Ichise, Masanori, Momosaki, Sotaro, Kudo, Gen, Ito, Fumitaka, Kato, Takashi, Yamaguchi, Hiroshi, Katada, Kazuhiro, Sawada, Makoto, Ito, Kengo
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container_end_page 424
container_issue 5
container_start_page 417
container_title Annals of nuclear medicine
container_volume 22
creator Toyama, Hiroshi
Hatano, Kentaro
Suzuki, Hiromi
Ichise, Masanori
Momosaki, Sotaro
Kudo, Gen
Ito, Fumitaka
Kato, Takashi
Yamaguchi, Hiroshi
Katada, Kazuhiro
Sawada, Makoto
Ito, Kengo
description Objective To investigate whether [ 11 C]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 [ 11 C]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 [ 11 C]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 [ 11 C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.
doi_str_mv 10.1007/s12149-008-0136-1
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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 [ 11 C]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 [ 11 C]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 &lt; 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 [ 11 C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.</description><identifier>ISSN: 0914-7187</identifier><identifier>EISSN: 1864-6433</identifier><identifier>DOI: 10.1007/s12149-008-0136-1</identifier><identifier>PMID: 18600420</identifier><language>eng</language><publisher>Japan: Springer Japan</publisher><subject>Animals ; Brain Injuries - chemically induced ; Brain Injuries - diagnostic imaging ; Brain Injuries - metabolism ; Carrier Proteins - metabolism ; Corpus Striatum - diagnostic imaging ; Corpus Striatum - metabolism ; Disease Models, Animal ; Ethanol ; Imaging ; Isoquinolines - pharmacokinetics ; Male ; Medicine ; Medicine &amp; Public Health ; Metabolic Clearance Rate ; Microglia - diagnostic imaging ; Microglia - metabolism ; Nuclear Medicine ; Original Article ; Positron-Emission Tomography - veterinary ; Radiology ; Radiopharmaceuticals - pharmacokinetics ; Rats ; Rats, Inbred F344 ; Receptors, GABA-A - metabolism ; Tissue Distribution</subject><ispartof>Annals of nuclear medicine, 2008-06, Vol.22 (5), p.417-424</ispartof><rights>The Japanese Society of Nuclear Medicine 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-c05c83de4812dae70520ef85513d92e902f199e3bf3a29e3fc7ca768df4b0ef23</citedby><cites>FETCH-LOGICAL-c519t-c05c83de4812dae70520ef85513d92e902f199e3bf3a29e3fc7ca768df4b0ef23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12149-008-0136-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12149-008-0136-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18600420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toyama, Hiroshi</creatorcontrib><creatorcontrib>Hatano, Kentaro</creatorcontrib><creatorcontrib>Suzuki, Hiromi</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Momosaki, Sotaro</creatorcontrib><creatorcontrib>Kudo, Gen</creatorcontrib><creatorcontrib>Ito, Fumitaka</creatorcontrib><creatorcontrib>Kato, Takashi</creatorcontrib><creatorcontrib>Yamaguchi, Hiroshi</creatorcontrib><creatorcontrib>Katada, Kazuhiro</creatorcontrib><creatorcontrib>Sawada, Makoto</creatorcontrib><creatorcontrib>Ito, Kengo</creatorcontrib><title>In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum</title><title>Annals of nuclear medicine</title><addtitle>Ann Nucl Med</addtitle><addtitle>Ann Nucl Med</addtitle><description>Objective To investigate whether [ 11 C]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 [ 11 C]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 [ 11 C]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 &lt; 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. 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Hatano, Kentaro ; Suzuki, Hiromi ; Ichise, Masanori ; Momosaki, Sotaro ; Kudo, Gen ; Ito, Fumitaka ; Kato, Takashi ; Yamaguchi, Hiroshi ; Katada, Kazuhiro ; Sawada, Makoto ; Ito, Kengo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-c05c83de4812dae70520ef85513d92e902f199e3bf3a29e3fc7ca768df4b0ef23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Brain Injuries - chemically induced</topic><topic>Brain Injuries - diagnostic imaging</topic><topic>Brain Injuries - metabolism</topic><topic>Carrier Proteins - metabolism</topic><topic>Corpus Striatum - diagnostic imaging</topic><topic>Corpus Striatum - metabolism</topic><topic>Disease Models, Animal</topic><topic>Ethanol</topic><topic>Imaging</topic><topic>Isoquinolines - pharmacokinetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metabolic Clearance Rate</topic><topic>Microglia - diagnostic imaging</topic><topic>Microglia - metabolism</topic><topic>Nuclear Medicine</topic><topic>Original Article</topic><topic>Positron-Emission Tomography - veterinary</topic><topic>Radiology</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptors, GABA-A - metabolism</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toyama, Hiroshi</creatorcontrib><creatorcontrib>Hatano, Kentaro</creatorcontrib><creatorcontrib>Suzuki, Hiromi</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Momosaki, Sotaro</creatorcontrib><creatorcontrib>Kudo, Gen</creatorcontrib><creatorcontrib>Ito, Fumitaka</creatorcontrib><creatorcontrib>Kato, Takashi</creatorcontrib><creatorcontrib>Yamaguchi, Hiroshi</creatorcontrib><creatorcontrib>Katada, Kazuhiro</creatorcontrib><creatorcontrib>Sawada, Makoto</creatorcontrib><creatorcontrib>Ito, Kengo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; 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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 [ 11 C]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 [ 11 C]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 &lt; 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 [ 11 C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.</abstract><cop>Japan</cop><pub>Springer Japan</pub><pmid>18600420</pmid><doi>10.1007/s12149-008-0136-1</doi><tpages>8</tpages></addata></record>
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subjects Animals
Brain Injuries - chemically induced
Brain Injuries - diagnostic imaging
Brain Injuries - metabolism
Carrier Proteins - metabolism
Corpus Striatum - diagnostic imaging
Corpus Striatum - metabolism
Disease Models, Animal
Ethanol
Imaging
Isoquinolines - pharmacokinetics
Male
Medicine
Medicine & Public Health
Metabolic Clearance Rate
Microglia - diagnostic imaging
Microglia - metabolism
Nuclear Medicine
Original Article
Positron-Emission Tomography - veterinary
Radiology
Radiopharmaceuticals - pharmacokinetics
Rats
Rats, Inbred F344
Receptors, GABA-A - metabolism
Tissue Distribution
title 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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