A probe for intracerebral aromatic amino‐acid decarboxylase activity: Distribution and kinetics of [18F]6‐fluoro‐L‐m‐tyrosine in the human brain
Identifieur interne : 005957 ( Main/Exploration ); précédent : 005956; suivant : 005958A probe for intracerebral aromatic amino‐acid decarboxylase activity: Distribution and kinetics of [18F]6‐fluoro‐L‐m‐tyrosine in the human brain
Auteurs : Nahmias [Canada] ; Lindi Wahl [Canada] ; Raman Chirakal [Canada] ; Gunter Firnau [Canada] ; E. Stephen Garnett [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 1995-05.
English descriptors
- KwdEn :
- Adolescent, Adult, Aromatic amino acid decarboxylase activity, Aromatic-L-Amino-Acid Decarboxylases (metabolism), Blood-Brain Barrier (drug effects), Blood-Brain Barrier (physiology), Brain (drug effects), Brain (enzymology), Brain (radionuclide imaging), Carbidopa (adverse effects), Carbidopa (therapeutic use), Compartmental analysis, Corpus Striatum (drug effects), Corpus Striatum (enzymology), Corpus Striatum (radionuclide imaging), Dopamine (metabolism), Female, Fluorine Radioisotopes (diagnostic use), Fluoro‐meta‐tyrosine, Humans, Image Processing, Computer-Assisted, Male, Parkinson Disease (drug therapy), Parkinson Disease (enzymology), Parkinson Disease (radionuclide imaging), Positron tomography, Reference Values, Tyrosine (analogs & derivatives), Tyrosine (diagnostic use), Tyrosine (pharmacokinetics).
- MESH :
- chemical , adverse effects : Carbidopa.
- chemical , analogs & derivatives : Tyrosine.
- chemical , diagnostic use : Fluorine Radioisotopes, Tyrosine.
- chemical , metabolism : Aromatic-L-Amino-Acid Decarboxylases, Dopamine.
- drug effects : Blood-Brain Barrier, Brain, Corpus Striatum.
- drug therapy : Parkinson Disease.
- enzymology : Brain, Corpus Striatum, Parkinson Disease.
- chemical , pharmacokinetics : Tyrosine.
- physiology : Blood-Brain Barrier.
- radionuclide imaging : Brain, Corpus Striatum, Parkinson Disease.
- chemical , therapeutic use : Carbidopa.
- Adolescent, Adult, Female, Humans, Image Processing, Computer-Assisted, Male, Reference Values.
Abstract
Positron tomography, using [18F]6‐fluoro‐L‐dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6‐fluoro‐L‐m‐tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine‐rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a twocompartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. decarboxylation rate constant (k21) was found to be 0.0108 min−1. Because the peripheral metabolism of FmT is simpler than that of [18F]6‐fluoro‐L‐dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.
Url:
DOI: 10.1002/mds.870100312
Affiliations:
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Stephen" last="Garnett">E. Stephen Garnett</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1995-05">1995-05</date><biblScope unit="vol">10</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="298">298</biblScope><biblScope unit="page" to="304">304</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">5B094FF6F0FD274ED22C0119A0F1E42AEA44773D</idno><idno type="DOI">10.1002/mds.870100312</idno><idno type="ArticleID">MDS870100312</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aromatic amino acid decarboxylase activity</term><term>Aromatic-L-Amino-Acid Decarboxylases (metabolism)</term><term>Blood-Brain Barrier (drug effects)</term><term>Blood-Brain Barrier (physiology)</term><term>Brain (drug effects)</term><term>Brain (enzymology)</term><term>Brain (radionuclide imaging)</term><term>Carbidopa (adverse effects)</term><term>Carbidopa (therapeutic use)</term><term>Compartmental analysis</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (enzymology)</term><term>Corpus Striatum (radionuclide imaging)</term><term>Dopamine (metabolism)</term><term>Female</term><term>Fluorine Radioisotopes (diagnostic use)</term><term>Fluoro‐meta‐tyrosine</term><term>Humans</term><term>Image Processing, Computer-Assisted</term><term>Male</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (enzymology)</term><term>Parkinson Disease (radionuclide imaging)</term><term>Positron tomography</term><term>Reference Values</term><term>Tyrosine (analogs & derivatives)</term><term>Tyrosine (diagnostic use)</term><term>Tyrosine (pharmacokinetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Carbidopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Tyrosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Fluorine Radioisotopes</term><term>Tyrosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Aromatic-L-Amino-Acid Decarboxylases</term><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood-Brain Barrier</term><term>Brain</term><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Tyrosine</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Blood-Brain Barrier</term></keywords><keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Brain</term><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Carbidopa</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Female</term><term>Humans</term><term>Image Processing, Computer-Assisted</term><term>Male</term><term>Reference Values</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Positron tomography, using [18F]6‐fluoro‐L‐dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6‐fluoro‐L‐m‐tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine‐rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a twocompartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. decarboxylation rate constant (k21) was found to be 0.0108 min−1. Because the peripheral metabolism of FmT is simpler than that of [18F]6‐fluoro‐L‐dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Nahmias" sort="Nahmias" uniqKey="Nahmias" last="Nahmias">Nahmias</name></noRegion><name sortKey="Chirakal, Raman" sort="Chirakal, Raman" uniqKey="Chirakal R" first="Raman" last="Chirakal">Raman Chirakal</name><name sortKey="Firnau, Gunter" sort="Firnau, Gunter" uniqKey="Firnau G" first="Gunter" last="Firnau">Gunter Firnau</name><name sortKey="Garnett, E Stephen" sort="Garnett, E Stephen" uniqKey="Garnett E" first="E. Stephen" last="Garnett">E. Stephen Garnett</name><name sortKey="Wahl, Lindi" sort="Wahl, Lindi" uniqKey="Wahl L" first="Lindi" last="Wahl">Lindi Wahl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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