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 |
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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 |
format | Article |
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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.</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 & 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
< 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><subject>Animals</subject><subject>Brain Injuries - chemically induced</subject><subject>Brain Injuries - diagnostic imaging</subject><subject>Brain Injuries - metabolism</subject><subject>Carrier Proteins - metabolism</subject><subject>Corpus Striatum - diagnostic imaging</subject><subject>Corpus Striatum - metabolism</subject><subject>Disease Models, Animal</subject><subject>Ethanol</subject><subject>Imaging</subject><subject>Isoquinolines - pharmacokinetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Clearance Rate</subject><subject>Microglia - diagnostic imaging</subject><subject>Microglia - metabolism</subject><subject>Nuclear Medicine</subject><subject>Original Article</subject><subject>Positron-Emission Tomography - veterinary</subject><subject>Radiology</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Tissue Distribution</subject><issn>0914-7187</issn><issn>1864-6433</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kcFu1DAQhi0EokvhAbggi0NvgRnH2Tjc0KpARSV6KCeEIm8ySb1y7GA7i9q34U3xaleqhMTBGsn_N_-M_TP2GuEdAtTvIwqUTQGgCsByXeATtkK1lsValuVTtoIGZVGjqs_Yixh3AEJVSjxnZxkCkAJW7M-V43uz99xMejRu5H7gk-mCH63Rlusumb1Oxju-xIOs-UzBzHcUsrol9-B7ox9oNo54oI7m5AO3ZtSu_8B_IG5-3nwtELGpeL7KJ8-x_Obylg_eWv_74EnpTjtvuXG7JdznwoNOPKZgdFqml-zZoG2kV6d6zr5_urzdfCmuv32-2ny8LroKm1R0UHWq7EkqFL2mGioBNKiqwrJvBDUgBmwaKrdDqUWuQ1d3ul6rfpDbDIrynF0cfefgfy0UUzuZ2JG12pFfYisQRQkSMvj2H3Dnl-DybpmpQFYKZYbwCOWvjDHQ0M4hPz3ctwjtIbz2GF6bw2sP4bWYe96cjJftRP1jxymtDIgjELPkRgqPk__v-hel0qXV</recordid><startdate>20080601</startdate><enddate>20080601</enddate><creator>Toyama, Hiroshi</creator><creator>Hatano, Kentaro</creator><creator>Suzuki, Hiromi</creator><creator>Ichise, Masanori</creator><creator>Momosaki, Sotaro</creator><creator>Kudo, Gen</creator><creator>Ito, Fumitaka</creator><creator>Kato, Takashi</creator><creator>Yamaguchi, Hiroshi</creator><creator>Katada, Kazuhiro</creator><creator>Sawada, Makoto</creator><creator>Ito, Kengo</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20080601</creationdate><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><author>Toyama, Hiroshi ; 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 & 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 & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest 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Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Annals of nuclear medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toyama, Hiroshi</au><au>Hatano, Kentaro</au><au>Suzuki, Hiromi</au><au>Ichise, Masanori</au><au>Momosaki, Sotaro</au><au>Kudo, Gen</au><au>Ito, Fumitaka</au><au>Kato, Takashi</au><au>Yamaguchi, Hiroshi</au><au>Katada, Kazuhiro</au><au>Sawada, Makoto</au><au>Ito, Kengo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum</atitle><jtitle>Annals of nuclear medicine</jtitle><stitle>Ann Nucl Med</stitle><addtitle>Ann Nucl Med</addtitle><date>2008-06-01</date><risdate>2008</risdate><volume>22</volume><issue>5</issue><spage>417</spage><epage>424</epage><pages>417-424</pages><issn>0914-7187</issn><eissn>1864-6433</eissn><abstract>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.</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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source | MEDLINE; Springer Nature - Complete Springer Journals |
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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