Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography
Identifieur interne : 002A27 ( Istex/Corpus ); précédent : 002A26; suivant : 002A28Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography
Auteurs : E. H. Danielsen ; D. F. Smith ; A. D. Gee ; T. K. Venkatachalam ; S. B. Hansen ; F. Hermansen ; A. Gjedde ; P. CummingSource :
- Synapse [ 0887-4476 ] ; 1999-09-15.
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Abstract
We measured 6‐[18F]fluoro‐L‐DOPA (FDOPA) uptake and metabolism in the brain of 4‐month‐old female pigs (n = 8) using a high‐resolution positron emission tomograph (PET) in 3D mode. The mean net blood–brain clearance of FDOPA (KiD) to striatum was 0.011 ml g‐1 min‐1. Correcting for the elimination of decarboxylated metabolites from striatum (kloss = 0.004 min‐1) increased the apparent magnitude of the estimate of KiD by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k3s) was 0.008 min‐1. For multicompartmental analyses, the FDOPA partition volume (VeD) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g‐1), with correction for the presence in brain of the plasma metabolite 3‐O‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k3D) was estimated to be 0.037 min‐1 in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of k3D in striatum. The magnitude of k3D in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k3D in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Synapse 33:247–258, 1999. © 1999 Wiley‐Liss, Inc.
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DOI: 10.1002/(SICI)1098-2396(19990915)33:4<247::AID-SYN1>3.0.CO;2-6
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H." last="Danielsen">E. H. Danielsen</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, Nørrebrogade 44, DK‐8000 Aarhus C, Denmark.</mods:affiliation></affiliation></author><author><name sortKey="Smith, D F" sort="Smith, D F" uniqKey="Smith D" first="D. F." last="Smith">D. F. Smith</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, DK‐8240 Risskov, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Gee, A D" sort="Gee, A D" uniqKey="Gee A" first="A. D." last="Gee">A. D. Gee</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Venkatachalam, T K" sort="Venkatachalam, T K" uniqKey="Venkatachalam T" first="T. K." last="Venkatachalam">T. K. Venkatachalam</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Hansen, S B" sort="Hansen, S B" uniqKey="Hansen S" first="S. B." last="Hansen">S. B. Hansen</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Hermansen, F" sort="Hermansen, F" uniqKey="Hermansen F" first="F." last="Hermansen">F. Hermansen</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A." last="Gjedde">A. Gjedde</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation><affiliation><mods:affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</mods:affiliation></affiliation></author><author><name sortKey="Cumming, P" sort="Cumming, P" uniqKey="Cumming P" first="P." last="Cumming">P. Cumming</name><affiliation><mods:affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</mods:affiliation></affiliation><affiliation><mods:affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1999-09-15">1999-09-15</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="247">247</biblScope><biblScope unit="page" to="258">258</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">B8C8D4A8EEA1BE1710F4C2593FF39321CE9CC2D6</idno><idno type="DOI">10.1002/(SICI)1098-2396(19990915)33:4<247::AID-SYN1>3.0.CO;2-6</idno><idno type="ArticleID">SYN1</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>6‐[18F]fluoro‐L‐DOPA</term><term>FDOPA</term><term>PET</term><term>dopamine</term><term>metabolic rates</term><term>neuroimaging</term><term>partial volume</term><term>positron emission tomography</term><term>swine / pigs / porcine striatum</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We measured 6‐[18F]fluoro‐L‐DOPA (FDOPA) uptake and metabolism in the brain of 4‐month‐old female pigs (n = 8) using a high‐resolution positron emission tomograph (PET) in 3D mode. The mean net blood–brain clearance of FDOPA (KiD) to striatum was 0.011 ml g‐1 min‐1. Correcting for the elimination of decarboxylated metabolites from striatum (kloss = 0.004 min‐1) increased the apparent magnitude of the estimate of KiD by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k3s) was 0.008 min‐1. For multicompartmental analyses, the FDOPA partition volume (VeD) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g‐1), with correction for the presence in brain of the plasma metabolite 3‐O‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k3D) was estimated to be 0.037 min‐1 in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of k3D in striatum. The magnitude of k3D in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k3D in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Synapse 33:247–258, 1999. © 1999 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>E.H. 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The mean net blood–brain clearance of FDOPA (KiD) to striatum was 0.011 ml g‐1 min‐1. Correcting for the elimination of decarboxylated metabolites from striatum (kloss = 0.004 min‐1) increased the apparent magnitude of the estimate of KiD by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k3s) was 0.008 min‐1. For multicompartmental analyses, the FDOPA partition volume (VeD) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g‐1), with correction for the presence in brain of the plasma metabolite 3‐O‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k3D) was estimated to be 0.037 min‐1 in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of k3D in striatum. The magnitude of k3D in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k3D in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. 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emission tomography</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><availability><p>Copyright © 1999 Wiley‐Liss, Inc.</p></availability><date>1999</date></publicationStmt><notesStmt><note>Danish Parkinson Foundation</note><note>Aarhus University Research Foundation</note><note>Danish Medical Society's Research Foundation</note><note>Novo Nordisk Foundation</note><note>Institute of Experimental Clinical Research at Aarhus University</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography</title><author xml:id="author-1"><persName><forename type="first">E.H.</forename><surname>Danielsen</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>PET‐Center, Aarhus University Hospital, Nørrebrogade 44, DK‐8000 Aarhus C, Denmark.</affiliation></author><author xml:id="author-2"><persName><forename type="first">D.F.</forename><surname>Smith</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, DK‐8240 Risskov, Denmark</affiliation></author><author xml:id="author-3"><persName><forename type="first">A.D.</forename><surname>Gee</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation></author><author xml:id="author-4"><persName><forename type="first">T.K.</forename><surname>Venkatachalam</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation></author><author xml:id="author-5"><persName><forename type="first">S.B.</forename><surname>Hansen</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation></author><author xml:id="author-6"><persName><forename type="first">F.</forename><surname>Hermansen</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation></author><author xml:id="author-7"><persName><forename type="first">A.</forename><surname>Gjedde</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</affiliation></author><author xml:id="author-8"><persName><forename type="first">P.</forename><surname>Cumming</surname></persName><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</affiliation></author></analytic><monogr><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="pISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><idno type="DOI">10.1002/(ISSN)1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1999-09-15"></date><biblScope unit="volume">33</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="247">247</biblScope><biblScope unit="page" to="258">258</biblScope></imprint></monogr><idno type="istex">B8C8D4A8EEA1BE1710F4C2593FF39321CE9CC2D6</idno><idno type="DOI">10.1002/(SICI)1098-2396(19990915)33:4<247::AID-SYN1>3.0.CO;2-6</idno><idno type="ArticleID">SYN1</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>We measured 6‐[18F]fluoro‐L‐DOPA (FDOPA) uptake and metabolism in the brain of 4‐month‐old female pigs (n = 8) using a high‐resolution positron emission tomograph (PET) in 3D mode. The mean net blood–brain clearance of FDOPA (KiD) to striatum was 0.011 ml g‐1 min‐1. Correcting for the elimination of decarboxylated metabolites from striatum (kloss = 0.004 min‐1) increased the apparent magnitude of the estimate of KiD by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k3s) was 0.008 min‐1. For multicompartmental analyses, the FDOPA partition volume (VeD) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g‐1), with correction for the presence in brain of the plasma metabolite 3‐O‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k3D) was estimated to be 0.037 min‐1 in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of k3D in striatum. The magnitude of k3D in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k3D in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Synapse 33:247–258, 1999. © 1999 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>6‐[18F]fluoro‐L‐DOPA</term></item><item><term>FDOPA</term></item><item><term>dopamine</term></item><item><term>metabolic rates</term></item><item><term>positron emission tomography</term></item><item><term>PET</term></item><item><term>neuroimaging</term></item><item><term>swine / pigs / porcine striatum</term></item><item><term>partial volume</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998-01-05">Received</change><change when="1998-11-17">Registration</change><change 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type="short">Synapse</title></titleGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/(SICI)1098-2396(19990915)33:4<>1.0.CO;2-F</doi><numberingGroup><numbering type="journalVolume" number="33">33</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="1999-09-15">15 September 1999</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="1" status="forIssue"><doi origin="wiley" registered="yes">10.1002/(SICI)1098-2396(19990915)33:4<247::AID-SYN1>3.0.CO;2-6</doi><idGroup><id type="unit" value="SYN1"></id></idGroup><countGroup><count type="pageTotal" number="12"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="publisher">Copyright © 1999 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="1998-01-05"></event><event type="manuscriptAccepted" date="1998-11-17"></event><event type="firstOnline" date="1999-07-23"></event><event type="publishedOnlineFinalForm" date="1999-07-23"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-04"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-10"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-11-03"></event></eventGroup><numberingGroup><numbering type="pageFirst">247</numbering><numbering type="pageLast">258</numbering></numberingGroup><correspondenceTo>PET‐Center, Aarhus University Hospital, Nørrebrogade 44, DK‐8000 Aarhus C, Denmark.</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:SYN.SYN1.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="6"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="58"></count><count type="wordTotal" number="8938"></count></countGroup><titleGroup><title type="main" xml:lang="en">Cerebral 6‐[<sup>18</sup>F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography</title><title type="short" xml:lang="en">FDOPA METABOLISM STUDIED BY PET</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>E.H.</givenNames><familyName>Danielsen</familyName></personName><contactDetails><email>erik@pet.auh.dk</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>D.F.</givenNames><familyName>Smith</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>A.D.</givenNames><familyName>Gee</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>T.K.</givenNames><familyName>Venkatachalam</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>S.B.</givenNames><familyName>Hansen</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>F.</givenNames><familyName>Hermansen</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1 #af3"><personName><givenNames>A.</givenNames><familyName>Gjedde</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1 #af3"><personName><givenNames>P.</givenNames><familyName>Cumming</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DK" type="organization"><unparsedAffiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DK" type="organization"><unparsedAffiliation>Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, DK‐8240 Risskov, Denmark</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="CA" type="organization"><unparsedAffiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">6‐[<sup>18</sup>F]fluoro‐L‐DOPA</keyword><keyword xml:id="kwd2">FDOPA</keyword><keyword xml:id="kwd3">dopamine</keyword><keyword xml:id="kwd4">metabolic rates</keyword><keyword xml:id="kwd5">positron emission tomography</keyword><keyword xml:id="kwd6">PET</keyword><keyword xml:id="kwd7">neuroimaging</keyword><keyword xml:id="kwd8">swine / pigs / porcine striatum</keyword><keyword xml:id="kwd9">partial volume</keyword></keywordGroup><fundingInfo><fundingAgency>Danish Parkinson Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Aarhus University Research Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Danish Medical Society's Research Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Novo Nordisk Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Institute of Experimental Clinical Research at Aarhus University</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>We measured 6‐[<sup>18</sup>F]fluoro‐L‐DOPA (FDOPA) uptake and metabolism in the brain of 4‐month‐old female pigs (n = 8) using a high‐resolution positron emission tomograph (PET) in 3D mode. The mean net blood–brain clearance of FDOPA (<i>K<sub>i</sub></i><i><sup>D</sup></i>) to striatum was 0.011 ml g<sup>‐1</sup> min<sup>‐1</sup>. Correcting for the elimination of decarboxylated metabolites from striatum (<i>k<sub>loss</sub></i> = 0.004 min<sup>‐1</sup>) increased the apparent magnitude of the estimate of <i>K<sub>i</sub></i><i><sup>D</sup></i> by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (<i>k<sub>3</sub></i><i><sup>s</sup></i>) was 0.008 min<sup>‐1</sup>. For multicompartmental analyses, the FDOPA partition volume (<i>V<sub>e</sub></i><i><sup>D</sup></i>) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g<sup>‐1</sup>), with correction for the presence in brain of the plasma metabolite 3‐<i>O</i>‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (<i>k<sub>3</sub></i><i><sup>D</sup></i>) was estimated to be 0.037 min<sup>‐1 </sup>in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of <i>k<sub>3</sub></i><i><sup>D</sup></i> in striatum. The magnitude of <i>k<sub>3</sub></i><i><sup>D</sup></i> in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of <i>k<sub>3</sub><sup>D</sup></i> in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Synapse 33:247–258, 1999. © 1999 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>FDOPA METABOLISM STUDIED BY PET</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography</title></titleInfo><name type="personal"><namePart type="given">E.H.</namePart><namePart type="family">Danielsen</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>PET‐Center, Aarhus University Hospital, Nørrebrogade 44, DK‐8000 Aarhus C, Denmark.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.F.</namePart><namePart type="family">Smith</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, DK‐8240 Risskov, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.D.</namePart><namePart type="family">Gee</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">T.K.</namePart><namePart type="family">Venkatachalam</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.B.</namePart><namePart type="family">Hansen</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Hermansen</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Gjedde</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Cumming</namePart><affiliation>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C, Denmark</affiliation><affiliation>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1999-09-15</dateIssued><dateCaptured encoding="w3cdtf">1998-01-05</dateCaptured><dateValid encoding="w3cdtf">1998-11-17</dateValid><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">6</extent><extent unit="tables">3</extent><extent unit="references">58</extent><extent unit="words">8938</extent></physicalDescription><abstract lang="en">We measured 6‐[18F]fluoro‐L‐DOPA (FDOPA) uptake and metabolism in the brain of 4‐month‐old female pigs (n = 8) using a high‐resolution positron emission tomograph (PET) in 3D mode. The mean net blood–brain clearance of FDOPA (KiD) to striatum was 0.011 ml g‐1 min‐1. Correcting for the elimination of decarboxylated metabolites from striatum (kloss = 0.004 min‐1) increased the apparent magnitude of the estimate of KiD by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxylation rate of FDOPA in striatum relative to the cerebellum input (k3s) was 0.008 min‐1. For multicompartmental analyses, the FDOPA partition volume (VeD) was constrained to the individual value observed in cerebellum (mean = 0.53 ml g‐1), with correction for the presence in brain of the plasma metabolite 3‐O‐methyl‐FDOPA (OMFD). Using the first 60 min of the dynamic PET scans, the rate constant of FDOPA decarboxylation (k3D) was estimated to be 0.037 min‐1 in striatum, but was not significantly different than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame‐sequence (120 min) increased the variance of the estimate of k3D in striatum. The magnitude of k3D in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI‐based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial resolution of our tomograph reduces the apparent magnitude of k3D in striatum. However, anaesthetised pigs are an appropriate experimental model for PET studies of DOPA decarboxylation in striatum. Synapse 33:247–258, 1999. © 1999 Wiley‐Liss, Inc.</abstract><note type="funding">Danish Parkinson Foundation</note><note type="funding">Aarhus University Research Foundation</note><note type="funding">Danish Medical Society's Research Foundation</note><note type="funding">Novo Nordisk Foundation</note><note type="funding">Institute of Experimental Clinical Research at Aarhus University</note><subject lang="en"><genre>keywords</genre><topic>6‐[18F]fluoro‐L‐DOPA</topic><topic>FDOPA</topic><topic>dopamine</topic><topic>metabolic rates</topic><topic>positron emission tomography</topic><topic>PET</topic><topic>neuroimaging</topic><topic>swine / pigs / porcine striatum</topic><topic>partial volume</topic></subject><relatedItem type="host"><titleInfo><title>Synapse</title></titleInfo><titleInfo type="abbreviated"><title>Synapse</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0887-4476</identifier><identifier type="eISSN">1098-2396</identifier><identifier type="DOI">10.1002/(ISSN)1098-2396</identifier><identifier type="PublisherID">SYN</identifier><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>33</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>247</start><end>258</end><total>12</total></extent></part></relatedItem><identifier type="istex">B8C8D4A8EEA1BE1710F4C2593FF39321CE9CC2D6</identifier><identifier type="DOI">10.1002/(SICI)1098-2396(19990915)33:4<247::AID-SYN1>3.0.CO;2-6</identifier><identifier type="ArticleID">SYN1</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1999 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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