A Within-Subject Comparison of 6-[18F]Fluoro-m-tyrosine and 6-[18F]Fluoro-l-dopa in Parkinson’s Disease
Identifieur interne : 000289 ( Pmc/Checkpoint ); précédent : 000288; suivant : 000290A Within-Subject Comparison of 6-[18F]Fluoro-m-tyrosine and 6-[18F]Fluoro-l-dopa in Parkinson’s Disease
Auteurs : Catherine L. Gallagher [États-Unis] ; Bradley T. Christian [États-Unis] ; James E. Holden [États-Unis] ; Onofre T. Dejesus [États-Unis] ; Robert J. Nickles [États-Unis] ; Laura Buyan-Dent [États-Unis] ; Barbara B. Bendlin [États-Unis] ; Sandra J. Harding [États-Unis] ; Charles K. Stone [États-Unis] ; Barb Mueller [États-Unis] ; Sterling C. Johnson [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2011.
Abstract
Progression of Parkinson’s disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[18F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[18F]fluoro-
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DOI: 10.1002/mds.23778
PubMed: 21638324
PubMed Central: 3278160
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Within-Subject Comparison of 6-[18F]Fluoro-m-tyrosine and 6-[18F]Fluoro-<sc>l</sc>-dopa in Parkinson’s Disease</title><author><name sortKey="Gallagher, Catherine L" sort="Gallagher, Catherine L" uniqKey="Gallagher C" first="Catherine L." last="Gallagher">Catherine L. Gallagher</name><affiliation wicri:level="2"><nlm:aff id="A1">William S. Middleton Veterans Hospital, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Christian, Bradley T" sort="Christian, Bradley T" uniqKey="Christian B" first="Bradley T." last="Christian">Bradley T. Christian</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Dejesus, Onofre T" sort="Dejesus, Onofre T" uniqKey="Dejesus O" first="Onofre T." last="Dejesus">Onofre T. Dejesus</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Nickles, Robert J" sort="Nickles, Robert J" uniqKey="Nickles R" first="Robert J." last="Nickles">Robert J. Nickles</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Buyan Dent, Laura" sort="Buyan Dent, Laura" uniqKey="Buyan Dent L" first="Laura" last="Buyan-Dent">Laura Buyan-Dent</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Bendlin, Barbara B" sort="Bendlin, Barbara B" uniqKey="Bendlin B" first="Barbara B." last="Bendlin">Barbara B. Bendlin</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Harding, Sandra J" sort="Harding, Sandra J" uniqKey="Harding S" first="Sandra J." last="Harding">Sandra J. Harding</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Stone, Charles K" sort="Stone, Charles K" uniqKey="Stone C" first="Charles K." last="Stone">Charles K. Stone</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Mueller, Barb" sort="Mueller, Barb" uniqKey="Mueller B" first="Barb" last="Mueller">Barb Mueller</name><affiliation wicri:level="2"><nlm:aff id="A4">Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Johnson, Sterling C" sort="Johnson, Sterling C" uniqKey="Johnson S" first="Sterling C." last="Johnson">Sterling C. Johnson</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21638324</idno><idno type="pmc">3278160</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278160</idno><idno type="RBID">PMC:3278160</idno><idno type="doi">10.1002/mds.23778</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000157</idno><idno type="wicri:Area/Pmc/Curation">000157</idno><idno type="wicri:Area/Pmc/Checkpoint">000289</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Within-Subject Comparison of 6-[18F]Fluoro-m-tyrosine and 6-[18F]Fluoro-<sc>l</sc>-dopa in Parkinson’s Disease</title><author><name sortKey="Gallagher, Catherine L" sort="Gallagher, Catherine L" uniqKey="Gallagher C" first="Catherine L." last="Gallagher">Catherine L. Gallagher</name><affiliation wicri:level="2"><nlm:aff id="A1">William S. Middleton Veterans Hospital, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Christian, Bradley T" sort="Christian, Bradley T" uniqKey="Christian B" first="Bradley T." last="Christian">Bradley T. Christian</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Dejesus, Onofre T" sort="Dejesus, Onofre T" uniqKey="Dejesus O" first="Onofre T." last="Dejesus">Onofre T. Dejesus</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Nickles, Robert J" sort="Nickles, Robert J" uniqKey="Nickles R" first="Robert J." last="Nickles">Robert J. Nickles</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Buyan Dent, Laura" sort="Buyan Dent, Laura" uniqKey="Buyan Dent L" first="Laura" last="Buyan-Dent">Laura Buyan-Dent</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Bendlin, Barbara B" sort="Bendlin, Barbara B" uniqKey="Bendlin B" first="Barbara B." last="Bendlin">Barbara B. Bendlin</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Harding, Sandra J" sort="Harding, Sandra J" uniqKey="Harding S" first="Sandra J." last="Harding">Sandra J. Harding</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Stone, Charles K" sort="Stone, Charles K" uniqKey="Stone C" first="Charles K." last="Stone">Charles K. Stone</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Mueller, Barb" sort="Mueller, Barb" uniqKey="Mueller B" first="Barb" last="Mueller">Barb Mueller</name><affiliation wicri:level="2"><nlm:aff id="A4">Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Johnson, Sterling C" sort="Johnson, Sterling C" uniqKey="Johnson S" first="Sterling C." last="Johnson">Sterling C. Johnson</name><affiliation wicri:level="2"><nlm:aff id="A5">William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author></analytic><series><title level="j">Movement Disorders</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Progression of Parkinson’s disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[<sup>18</sup>F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa. The objective of this study was to evaluate 6-[<sup>18</sup>F]fluoro-m-tyrosine relative to 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa with partial catechol-<italic>O</italic>-methyltransferase inhibition as a biomarker for clinical status in Parkinson’s disease. Twelve patients with early-stage Parkinson’s disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3-dimensional dynamic positron emission tomography using equivalent doses of 6-[<sup>18</sup>F]fluoro-m-tyrosine and 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa with tolcapone, a catechol-<italic>O</italic>-methyltransferase inhibitor. Images were realigned within subject, after which the tissue-derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue-derived uptake rate constant. Tissue-derived uptake rate constant values were correlated between the radiopharmaceuticals (<italic>r</italic> = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6-[<sup>18</sup>F]fluoro-m-tyrosine tissue-derived uptake rate constant (|r| > 0.72, <italic>P</italic> < .005) but not significantly with the 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa tissue- derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6-[<sup>18</sup>F]fluoro-m-tyrosine. In this design, 6-[<sup>18</sup>F]fluoro-m-tyrosine uptake better reflected clinical status than did 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa uptake. We attribute this finding to 6-[<sup>18</sup>F]fluoro-m-tyrosine’s higher affinity for the target, <sc>l</sc>-aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that <sc>l</sc>-aromatic amino acid decarboxylase activity is a major determinant of clinical status.</p></div></front></TEI><pmc article-type="research-article" xml:lang="en"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8610688</journal-id><journal-id journal-id-type="pubmed-jr-id">5937</journal-id><journal-id journal-id-type="nlm-ta">Mov Disord</journal-id><journal-title-group><journal-title>Movement Disorders</journal-title></journal-title-group><issn pub-type="ppub">0885-3185</issn><issn pub-type="epub">1531-8257</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21638324</article-id><article-id pub-id-type="pmc">3278160</article-id><article-id pub-id-type="doi">10.1002/mds.23778</article-id><article-id pub-id-type="manuscript">NIHMS352210</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A Within-Subject Comparison of 6-[18F]Fluoro-m-tyrosine and 6-[18F]Fluoro-<sc>l</sc>-dopa in Parkinson’s Disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gallagher</surname><given-names>Catherine L.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Christian</surname><given-names>Bradley T.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Holden</surname><given-names>James E.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Dejesus</surname><given-names>Onofre T.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Nickles</surname><given-names>Robert J.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Buyan-Dent</surname><given-names>Laura</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bendlin</surname><given-names>Barbara B.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Harding</surname><given-names>Sandra J.</given-names></name><degrees>MS</degrees><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Stone</surname><given-names>Charles K.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Mueller</surname><given-names>Barb</given-names></name><degrees>BS</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Sterling C.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib></contrib-group><aff id="A1"><label>1</label>William S. Middleton Veterans Hospital, Madison, Wisconsin, USA</aff><aff id="A2"><label>2</label>Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</aff><aff id="A3"><label>3</label>University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA</aff><aff id="A4"><label>4</label>Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA</aff><aff id="A5"><label>5</label>William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA</aff><aff id="A6"><label>6</label>Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA</aff><author-notes><corresp id="cor1"><label>*</label><bold>Correspondence to:</bold> Dr. Catherine L. Gallagher, William S. Middleton V.A. and University of Wisconsin Department of Neurology, 2500 Overlook Terrace Dr., Madison, WI, 53705, USA; <email>gallagher@neurology.wisc.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>3</day><month>2</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>2</day><month>6</month><year>2011</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>13</day><month>2</month><year>2012</year></pub-date><volume>26</volume><issue>11</issue><fpage>2032</fpage><lpage>2038</lpage><permissions><copyright-statement>© 2011 <italic>Movement</italic> Disorder Society</copyright-statement><copyright-year>2011</copyright-year></permissions><abstract><p id="P1">Progression of Parkinson’s disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[<sup>18</sup>F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa. The objective of this study was to evaluate 6-[<sup>18</sup>F]fluoro-m-tyrosine relative to 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa with partial catechol-<italic>O</italic>-methyltransferase inhibition as a biomarker for clinical status in Parkinson’s disease. Twelve patients with early-stage Parkinson’s disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3-dimensional dynamic positron emission tomography using equivalent doses of 6-[<sup>18</sup>F]fluoro-m-tyrosine and 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa with tolcapone, a catechol-<italic>O</italic>-methyltransferase inhibitor. Images were realigned within subject, after which the tissue-derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue-derived uptake rate constant. Tissue-derived uptake rate constant values were correlated between the radiopharmaceuticals (<italic>r</italic> = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6-[<sup>18</sup>F]fluoro-m-tyrosine tissue-derived uptake rate constant (|r| > 0.72, <italic>P</italic> < .005) but not significantly with the 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa tissue- derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6-[<sup>18</sup>F]fluoro-m-tyrosine. In this design, 6-[<sup>18</sup>F]fluoro-m-tyrosine uptake better reflected clinical status than did 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-dopa uptake. We attribute this finding to 6-[<sup>18</sup>F]fluoro-m-tyrosine’s higher affinity for the target, <sc>l</sc>-aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that <sc>l</sc>-aromatic amino acid decarboxylase activity is a major determinant of clinical status.</p></abstract><kwd-group><kwd>positron emission tomography</kwd><kwd>Parkinson’s disease/radionuclide imaging</kwd><kwd>dopamine/metabolism</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Center for Research Resources : NCRR</funding-source><award-id>UL1 RR025011-05 || RR</award-id></award-group><award-group><funding-source country="United States">National Center for Research Resources : NCRR</funding-source><award-id>UL1 RR025011-04 || RR</award-id></award-group><award-group><funding-source country="United States">National Center for Research Resources : NCRR</funding-source><award-id>UL1 RR025011-03 || RR</award-id></award-group></funding-group></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Wisconsin</li></region></list><tree><country name="États-Unis"><region name="Wisconsin"><name sortKey="Gallagher, Catherine L" sort="Gallagher, Catherine L" uniqKey="Gallagher C" first="Catherine L." last="Gallagher">Catherine L. Gallagher</name></region><name sortKey="Bendlin, Barbara B" sort="Bendlin, Barbara B" uniqKey="Bendlin B" first="Barbara B." last="Bendlin">Barbara B. Bendlin</name><name sortKey="Bendlin, Barbara B" sort="Bendlin, Barbara B" uniqKey="Bendlin B" first="Barbara B." last="Bendlin">Barbara B. Bendlin</name><name sortKey="Buyan Dent, Laura" sort="Buyan Dent, Laura" uniqKey="Buyan Dent L" first="Laura" last="Buyan-Dent">Laura Buyan-Dent</name><name sortKey="Christian, Bradley T" sort="Christian, Bradley T" uniqKey="Christian B" first="Bradley T." last="Christian">Bradley T. Christian</name><name sortKey="Christian, Bradley T" sort="Christian, Bradley T" uniqKey="Christian B" first="Bradley T." last="Christian">Bradley T. Christian</name><name sortKey="Dejesus, Onofre T" sort="Dejesus, Onofre T" uniqKey="Dejesus O" first="Onofre T." last="Dejesus">Onofre T. Dejesus</name><name sortKey="Gallagher, Catherine L" sort="Gallagher, Catherine L" uniqKey="Gallagher C" first="Catherine L." last="Gallagher">Catherine L. Gallagher</name><name sortKey="Harding, Sandra J" sort="Harding, Sandra J" uniqKey="Harding S" first="Sandra J." last="Harding">Sandra J. Harding</name><name sortKey="Harding, Sandra J" sort="Harding, Sandra J" uniqKey="Harding S" first="Sandra J." last="Harding">Sandra J. Harding</name><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name><name sortKey="Johnson, Sterling C" sort="Johnson, Sterling C" uniqKey="Johnson S" first="Sterling C." last="Johnson">Sterling C. Johnson</name><name sortKey="Johnson, Sterling C" sort="Johnson, Sterling C" uniqKey="Johnson S" first="Sterling C." last="Johnson">Sterling C. Johnson</name><name sortKey="Mueller, Barb" sort="Mueller, Barb" uniqKey="Mueller B" first="Barb" last="Mueller">Barb Mueller</name><name sortKey="Nickles, Robert J" sort="Nickles, Robert J" uniqKey="Nickles R" first="Robert J." last="Nickles">Robert J. Nickles</name><name sortKey="Stone, Charles K" sort="Stone, Charles K" uniqKey="Stone C" first="Charles K." last="Stone">Charles K. Stone</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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