The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM
PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared thes...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2021-03, Vol.41 (3), p.617-629 |
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| creator | Little, Philip V Arnberg, Fabian Jussing, Emma Lu, Li Ingemann Jensen, Andreas Mitsios, Nicholas Mulder, Jan Tran, Thuy A Holmin, Staffan |
| description | PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS. |
| doi_str_mv | 10.1177/0271678X20923857 |
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[18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1177/0271678X20923857</identifier><identifier>PMID: 32423333</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Astrocytes - chemistry ; Astrocytes - metabolism ; Autoradiography ; Brain - diagnostic imaging ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cerebellar Cortex - chemistry ; Cerebellar Cortex - diagnostic imaging ; Cerebellar Cortex - pathology ; Coordination Complexes ; Copper Radioisotopes - chemistry ; Disease Models, Animal ; Fluorine Radioisotopes - chemistry ; Hypoxia ; Male ; Misonidazole - analogs & derivatives ; Misonidazole - chemical synthesis ; Misonidazole - chemistry ; Neurons - chemistry ; Neurons - metabolism ; Organometallic Compounds - chemical synthesis ; Organometallic Compounds - chemistry ; Original ; Positron-Emission Tomography ; Radiopharmaceuticals - chemical synthesis ; Radiopharmaceuticals - chemistry ; Rats ; Rats, Sprague-Dawley ; Thiosemicarbazones - chemical synthesis ; Thiosemicarbazones - chemistry</subject><ispartof>Journal of cerebral blood flow and metabolism, 2021-03, Vol.41 (3), p.617-629</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020 2020 International Society for Cerebral Blood Flow and Metabolism</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-bb51ba129826aab6349aa447a24af030c6e9e7c5eeaafeddd0dd13d347c136533</citedby><cites>FETCH-LOGICAL-c439t-bb51ba129826aab6349aa447a24af030c6e9e7c5eeaafeddd0dd13d347c136533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922752/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922752/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,552,725,778,782,883,21808,27913,27914,43610,43611,53780,53782</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32423333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:143773731$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Little, Philip V</creatorcontrib><creatorcontrib>Arnberg, Fabian</creatorcontrib><creatorcontrib>Jussing, Emma</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Ingemann Jensen, Andreas</creatorcontrib><creatorcontrib>Mitsios, Nicholas</creatorcontrib><creatorcontrib>Mulder, Jan</creatorcontrib><creatorcontrib>Tran, Thuy A</creatorcontrib><creatorcontrib>Holmin, Staffan</creatorcontrib><title>The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.</description><subject>Animals</subject><subject>Astrocytes - chemistry</subject><subject>Astrocytes - metabolism</subject><subject>Autoradiography</subject><subject>Brain - diagnostic imaging</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cerebellar Cortex - chemistry</subject><subject>Cerebellar Cortex - diagnostic imaging</subject><subject>Cerebellar Cortex - pathology</subject><subject>Coordination Complexes</subject><subject>Copper Radioisotopes - chemistry</subject><subject>Disease Models, Animal</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Hypoxia</subject><subject>Male</subject><subject>Misonidazole - analogs & derivatives</subject><subject>Misonidazole - chemical synthesis</subject><subject>Misonidazole - chemistry</subject><subject>Neurons - chemistry</subject><subject>Neurons - metabolism</subject><subject>Organometallic Compounds - chemical synthesis</subject><subject>Organometallic Compounds - chemistry</subject><subject>Original</subject><subject>Positron-Emission Tomography</subject><subject>Radiopharmaceuticals - chemical synthesis</subject><subject>Radiopharmaceuticals - chemistry</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Thiosemicarbazones - chemical synthesis</subject><subject>Thiosemicarbazones - chemistry</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp1Udtq3DAQFaWl2aR971PRD7jRxbLsl0JYsm0gIYVsoRCCGUvjWInXMpLdbf6gn10tm4ak0HmZQecyaA4hHzj7xLnWx0xoXujyh2CVkKXSr8iCK1VlmvHiNVns4GyHH5DDGO8YY6VU6i05kCIXMtWC_F53SA32_dxDoA1EF6lvqRtMQIho6bfTNe0eRv_LAZ0CGAx0Hie4x8ShrTfQJ3nAJqTBRdPhJhG3buqo8ZsRgot-oA1OW8SBXvNydbO6OLu6pDBYel3ky_lmOZ-sry7ekTct9BHfP_Yj8n11ul5-zc4vv5wtT84zk8tqyppG8Qa4qEpRADSFzCuAPNcgcmiZZKbACrVRiAAtWmuZtVxamWvDZaGkPCLZ3jducZybegxuA-Gh9uDqx6f7NGGday7Yjv95z0_IBq3BIV2hfyF7iQyuq2_9z1pXQmglkgHbG5jgYwzYPmk5q3cp1v-mmCQfn-98EvyN7dkn4BbrOz-HId3s_4Z_AOx0qB0</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Little, Philip V</creator><creator>Arnberg, Fabian</creator><creator>Jussing, Emma</creator><creator>Lu, Li</creator><creator>Ingemann Jensen, Andreas</creator><creator>Mitsios, Nicholas</creator><creator>Mulder, Jan</creator><creator>Tran, Thuy A</creator><creator>Holmin, Staffan</creator><general>SAGE Publications</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>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20210301</creationdate><title>The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM</title><author>Little, Philip V ; Arnberg, Fabian ; Jussing, Emma ; Lu, Li ; Ingemann Jensen, Andreas ; Mitsios, Nicholas ; Mulder, Jan ; Tran, Thuy A ; Holmin, Staffan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-bb51ba129826aab6349aa447a24af030c6e9e7c5eeaafeddd0dd13d347c136533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Astrocytes - chemistry</topic><topic>Astrocytes - metabolism</topic><topic>Autoradiography</topic><topic>Brain - diagnostic imaging</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Cerebellar Cortex - chemistry</topic><topic>Cerebellar Cortex - diagnostic imaging</topic><topic>Cerebellar Cortex - pathology</topic><topic>Coordination Complexes</topic><topic>Copper Radioisotopes - chemistry</topic><topic>Disease Models, Animal</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Hypoxia</topic><topic>Male</topic><topic>Misonidazole - analogs & derivatives</topic><topic>Misonidazole - chemical synthesis</topic><topic>Misonidazole - chemistry</topic><topic>Neurons - chemistry</topic><topic>Neurons - metabolism</topic><topic>Organometallic Compounds - chemical synthesis</topic><topic>Organometallic Compounds - chemistry</topic><topic>Original</topic><topic>Positron-Emission Tomography</topic><topic>Radiopharmaceuticals - chemical synthesis</topic><topic>Radiopharmaceuticals - chemistry</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Thiosemicarbazones - chemical synthesis</topic><topic>Thiosemicarbazones - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Little, Philip V</creatorcontrib><creatorcontrib>Arnberg, Fabian</creatorcontrib><creatorcontrib>Jussing, Emma</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Ingemann Jensen, Andreas</creatorcontrib><creatorcontrib>Mitsios, Nicholas</creatorcontrib><creatorcontrib>Mulder, Jan</creatorcontrib><creatorcontrib>Tran, Thuy A</creatorcontrib><creatorcontrib>Holmin, Staffan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of cerebral blood flow and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Little, Philip V</au><au>Arnberg, Fabian</au><au>Jussing, Emma</au><au>Lu, Li</au><au>Ingemann Jensen, Andreas</au><au>Mitsios, Nicholas</au><au>Mulder, Jan</au><au>Tran, Thuy A</au><au>Holmin, Staffan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM</atitle><jtitle>Journal of cerebral blood flow and metabolism</jtitle><addtitle>J Cereb Blood Flow Metab</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>41</volume><issue>3</issue><spage>617</spage><epage>629</epage><pages>617-629</pages><issn>0271-678X</issn><eissn>1559-7016</eissn><abstract>PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>32423333</pmid><doi>10.1177/0271678X20923857</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Astrocytes - chemistry Astrocytes - metabolism Autoradiography Brain - diagnostic imaging Brain Ischemia - metabolism Brain Ischemia - pathology Cerebellar Cortex - chemistry Cerebellar Cortex - diagnostic imaging Cerebellar Cortex - pathology Coordination Complexes Copper Radioisotopes - chemistry Disease Models, Animal Fluorine Radioisotopes - chemistry Hypoxia Male Misonidazole - analogs & derivatives Misonidazole - chemical synthesis Misonidazole - chemistry Neurons - chemistry Neurons - metabolism Organometallic Compounds - chemical synthesis Organometallic Compounds - chemistry Original Positron-Emission Tomography Radiopharmaceuticals - chemical synthesis Radiopharmaceuticals - chemistry Rats Rats, Sprague-Dawley Thiosemicarbazones - chemical synthesis Thiosemicarbazones - chemistry |
| title | The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM |
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