Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography
Identifieur interne : 003773 ( Main/Exploration ); précédent : 003772; suivant : 003774Cerebral 6‐[18F]fluoro‐L‐DOPA (FDOPA) metabolism in pig studied by positron emission tomography
Auteurs : E. H. Danielsen [Danemark] ; D. F. Smith [Danemark] ; A. D. Gee [Danemark] ; T. K. Venkatachalam [Danemark] ; S. B. Hansen [Danemark] ; F. Hermansen [Danemark] ; A. Gjedde [Danemark, Canada] ; P. Cumming [Danemark, Canada]Source :
- 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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Venkatachalam</name><affiliation wicri:level="1"><country xml:lang="fr">Danemark</country><wicri:regionArea>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK‐8000 Aarhus C</wicri:noRegion></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 wicri:level="1"><country xml:lang="fr">Danemark</country><wicri:regionArea>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK‐8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Hermansen, F" sort="Hermansen, F" uniqKey="Hermansen F" first="F." last="Hermansen">F. Hermansen</name><affiliation wicri:level="1"><country xml:lang="fr">Danemark</country><wicri:regionArea>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK‐8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A." last="Gjedde">A. Gjedde</name><affiliation wicri:level="1"><country xml:lang="fr">Danemark</country><wicri:regionArea>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK‐8000 Aarhus C</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Canada</country><wicri:regionArea>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Cumming, P" sort="Cumming, P" uniqKey="Cumming P" first="P." last="Cumming">P. Cumming</name><affiliation wicri:level="1"><country xml:lang="fr">Danemark</country><wicri:regionArea>PET‐Center, Aarhus University Hospital, DK‐8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK‐8000 Aarhus C</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Canada</country><wicri:regionArea>McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></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><affiliations><list><country><li>Canada</li><li>Danemark</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement></list><tree><country name="Danemark"><noRegion><name sortKey="Danielsen, E H" sort="Danielsen, E H" uniqKey="Danielsen E" first="E. H." last="Danielsen">E. H. Danielsen</name></noRegion><name sortKey="Cumming, P" sort="Cumming, P" uniqKey="Cumming P" first="P." last="Cumming">P. Cumming</name><name sortKey="Danielsen, E H" sort="Danielsen, E H" uniqKey="Danielsen E" first="E. H." last="Danielsen">E. H. Danielsen</name><name sortKey="Gee, A D" sort="Gee, A D" uniqKey="Gee A" first="A. D." last="Gee">A. D. Gee</name><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A." last="Gjedde">A. Gjedde</name><name sortKey="Hansen, S B" sort="Hansen, S B" uniqKey="Hansen S" first="S. B." last="Hansen">S. B. Hansen</name><name sortKey="Hermansen, F" sort="Hermansen, F" uniqKey="Hermansen F" first="F." last="Hermansen">F. Hermansen</name><name sortKey="Smith, D F" sort="Smith, D F" uniqKey="Smith D" first="D. F." last="Smith">D. F. Smith</name><name sortKey="Smith, D F" sort="Smith, D F" uniqKey="Smith D" first="D. F." last="Smith">D. F. Smith</name><name sortKey="Venkatachalam, T K" sort="Venkatachalam, T K" uniqKey="Venkatachalam T" first="T. K." last="Venkatachalam">T. K. Venkatachalam</name></country><country name="Canada"><region name="Québec"><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A." last="Gjedde">A. Gjedde</name></region><name sortKey="Cumming, P" sort="Cumming, P" uniqKey="Cumming P" first="P." last="Cumming">P. Cumming</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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