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Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques

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dc.contributor.author Brown C.A.
dc.contributor.author Karimi M.K.
dc.contributor.author Tian L.
dc.contributor.author Flores H.
dc.contributor.author Su Y.
dc.contributor.author Tabbal S.D.
dc.contributor.author Loftin S.K.
dc.contributor.author Moerlein S.M.
dc.contributor.author Perlmutter J.S.
dc.contributor.editor
dc.date Oct-2013
dc.date.accessioned 2017-10-05T15:40:10Z
dc.date.available 2017-10-05T15:40:10Z
dc.date.issued 2013
dc.identifier 10.1002/ana.23939
dc.identifier.isbn
dc.identifier.issn 03645134
dc.identifier.uri http://hdl.handle.net/10938/17278
dc.description.abstract Objective: Development of an effective therapy to slow the inexorable progression of Parkinson disease requires a reliable, objective measurement of disease severity. In the present study, we compare presynaptic positron emission tomography (PET) tracer uptake in the substantia nigra (SN) to cell loss and motor impairment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates. Methods: Presynaptic PET tracers 6-[18F]- fluorodopa (FD), [11C]-2β-methoxy-3β-4-fluorophenyltropane (CFT), and [11C]-dihydrotetrabenazine (DTBZ) were used to measure specific uptake in the SN and striatum before and after a variable dose of MPTP in nonhuman primates. These in vivo PET-based measures were compared with motor impairment, as well as postmortem tyrosine hydroxylase-positive cell counts and striatal dopamine concentration. Results: We found the specific uptake of both CFT and DTBZ in the SN had a strong, significant correlation with dopaminergic cell counts in the SN (R2 = 0.77, 0.53, respectively, p andlt; 0.001), but uptake of FD did not. Additionally, both CFT and DTBZ specific uptake in the SN had a linear relationship with motor impairment (rs = -0.77, -0.71, respectively, p andlt; 0.001), but FD uptake did not. Interpretation: Our findings demonstrate that PET-measured binding potentials for CFT and DTBZ for a midbrain volume of interest targeted at the SN provide faithful correlates of nigral neuronal counts across a full range of lesion severity. Because these measures correlate with both nigral cell counts and parkinsonian ratings, we suggest that these SN PET measures are relevant biomarkers of nigrostriatal function. © 2013 American Neurological Association.
dc.format.extent
dc.format.extent Pages: (602-610)
dc.language English
dc.publisher HOBOKEN
dc.relation.ispartof Publication Name: Annals of Neurology; Publication Year: 2013; Volume: 74; no. 4; Pages: (602-610);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques
dc.type Article
dc.contributor.affiliation Brown, C.A., Department of Neurology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Karimi, M.K., Department of Neurology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Tian, L., Department of Neurology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Flores, H., Department of Neurology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Su, Y., Department of Radiology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Tabbal, S.D., Department of Neurology, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Loftin, S.K., Department of Neurology, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Moerlein, S.M., Department of Radiology, Washington University of Medicine, St Louis, MO, United States, Department of Biochemistry and Molecular Biophysics, Washington University of Medicine, St Louis, MO, United States
dc.contributor.affiliation Perlmutter, J.S., Department of Neurology, Washington University of Medicine, St Louis, MO, United States, Department of Radiology, Washington University of Medicine, St Louis, MO, United States, Department of Neurobiology, Washington University of Medicine, St Louis, MO, United States, Department of Occupational Therapy, Washington University of Medicine, St Louis, MO, United States, Department of Physical Therapy, Washington University of Medicine, St Louis, MO, United States
dc.contributor.authorAddress Perlmutter, J.S.; Washington University, School of Medicine, 660 South Euclid, Campus Box 8111, St Louis, MO 63110, United States; email: joel@npg.wustl.edu
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Internal Medicine; Division: Neurology;
dc.contributor.authorDepartment Internal Medicine
dc.contributor.authorDivision Neurology
dc.contributor.authorEmail joel@npg.wustl.edu
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Brown, CA
dc.contributor.authorInitials Karimi, MK
dc.contributor.authorInitials Tian, LL
dc.contributor.authorInitials Flores, H
dc.contributor.authorInitials Su, Y
dc.contributor.authorInitials Tabbal, SD
dc.contributor.authorInitials Loftin, SK
dc.contributor.authorInitials Moerlein, SM
dc.contributor.authorInitials Perlmutter, JS
dc.contributor.authorOrcidID Tian, LinLin-0000-0001-9504-1718
dc.contributor.authorReprintAddress Perlmutter, JS (reprint author), Washington Univ, Sch Med, 660 South Euclid,Campus Box 8111, St Louis, MO 63110 USA.
dc.contributor.authorResearcherID Tian, LinLin-A-5861-2012
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 1
dc.description.citedTotWOSCount 5
dc.description.citedWOSCount 5
dc.format.extentCount 9
dc.identifier.articleNo
dc.identifier.coden ANNED
dc.identifier.pubmedID 23686841
dc.identifier.scopusID 84890123415
dc.identifier.url
dc.publisher.address 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency NS058714, NINDS, National Institute of Neurological Disorders and Stroke
dc.relation.ispartofFundingAgency NS069746, NINDS, National Institute of Neurological Disorders and Stroke
dc.relation.ispartofFundingAgency NS041509, NINDS, National Institute of Neurological Disorders and Stroke
dc.relation.ispartofFundingAgency NS075321, NINDS, National Institu
dc.relation.ispartOfISOAbbr Ann. Neurol.
dc.relation.ispartOfIssue 4
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Annals of Neurology
dc.relation.ispartofPubTitleAbbr Ann. Neurol.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 74
dc.source.ID WOS:000327369100014
dc.type.publication Journal
dc.subject.otherAuthKeyword
dc.subject.otherChemCAS 1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine, 28289-54-5
dc.subject.otherChemCAS 6 fluorodopa f 18, 92812-82-3
dc.subject.otherChemCAS carbon 11, 14333-33-6
dc.subject.otherChemCAS dihydrotetrabenazine, 3466-75-9
dc.subject.otherChemCAS dopamine, 51-61-6, 62-31-7
dc.subject.otherChemCAS tyrosine 3 monooxygenase, 9036-22-0
dc.subject.otherChemCAS Carbon Isotopes
dc.subject.otherChemCAS Fluorodeoxyglucose F18, 0Z5B2CJX4D
dc.subject.otherChemCAS Tetrabenazine, Z9O08YRN8O
dc.subject.otherChemCAS dihydrotetrabenazine, 3466-75-9
dc.subject.otherIndex 1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine
dc.subject.otherIndex 2beta methoxy 3beta 4 fluorophenyltropane c 11
dc.subject.otherIndex 6 fluorodopa f 18
dc.subject.otherIndex carbon 11
dc.subject.otherIndex dihydrotetrabenazine
dc.subject.otherIndex dihydrotetrabenazine c 11
dc.subject.otherIndex dopamine
dc.subject.otherIndex tyrosine 3 monooxygenase
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex animal experiment
dc.subject.otherIndex article
dc.subject.otherIndex brain size
dc.subject.otherIndex controlled study
dc.subject.otherIndex corpus striatum
dc.subject.otherIndex correlation analysis
dc.subject.otherIndex dopamine brain level
dc.subject.otherIndex Macaca
dc.subject.otherIndex male
dc.subject.otherIndex mesencephalon
dc.subject.otherIndex motor dysfunction
dc.subject.otherIndex nerve cell necrosis
dc.subject.otherIndex nigroneostriatal system
dc.subject.otherIndex nonhuman
dc.subject.otherIndex Parkinson disease
dc.subject.otherIndex positron emission tomography
dc.subject.otherIndex priority journal
dc.subject.otherIndex substantia nigra
dc.subject.otherIndex validation study
dc.subject.otherIndex Animals
dc.subject.otherIndex Carbon Isotopes
dc.subject.otherIndex Disease Models, Animal
dc.subject.otherIndex Fluorodeoxyglucose F18
dc.subject.otherIndex Macaca mulatta
dc.subject.otherIndex Magnetic Resonance Imaging
dc.subject.otherIndex Male
dc.subject.otherIndex Mesencephalon
dc.subject.otherIndex MPTP Poisoning
dc.subject.otherIndex Neurons
dc.subject.otherIndex Positron-Emission Tomography
dc.subject.otherIndex Substantia Nigra
dc.subject.otherIndex Tetrabenazine
dc.subject.otherKeywordPlus BRAIN TRANSFER CONSTANTS
dc.subject.otherKeywordPlus TIME UPTAKE DATA
dc.subject.otherKeywordPlus PARKINSONS-DISEASE
dc.subject.otherKeywordPlus DOPAMINE TRANSPORTER
dc.subject.otherKeywordPlus GRAPHICAL EVALUATION
dc.subject.otherKeywordPlus SUBSTANTIA-NIGRA
dc.subject.otherKeywordPlus PRIMATE MODEL
dc.subject.otherKeywordPlus PET
dc.subject.otherKeywordPlus LOCALIZATION
dc.subject.otherKeywordPlus PERFORMANCE
dc.subject.otherWOS Clinical Neurology
dc.subject.otherWOS Neurosciences


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