{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T08:44:19Z","timestamp":1772095459123,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,9,16]],"date-time":"2013-09-16T00:00:00Z","timestamp":1379289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010treated nonhuman primates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Presynaptic PET tracers 6\u2010[<jats:sup>18<\/jats:sup>F]\u2010fluorodopa (FD), [<jats:sup>11<\/jats:sup>C]\u20102\u03b2\u2010methoxy\u20103\u03b2\u20104\u2010fluorophenyltropane (CFT), and [<jats:sup>11<\/jats:sup>C]\u2010dihydrotetrabenazine (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\u2010based measures were compared with motor impairment, as well as postmortem tyrosine hydroxylase\u2010positive cell counts and striatal dopamine concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.77, 0.53, respectively, <jats:italic>p<\/jats:italic> &lt; 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 (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic> = \u22120.77, \u22120.71, respectively, <jats:italic>p<\/jats:italic> &lt; 0.001), but FD uptake did not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings demonstrate that PET\u2010measured 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. Ann Neurol 2013;74:602\u2013610<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.23939","type":"journal-article","created":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T08:14:53Z","timestamp":1369037693000},"page":"602-610","source":"Crossref","is-referenced-by-count":38,"title":["Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques"],"prefix":"10.1002","volume":"74","author":[{"given":"Christopher A.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morvarid K.","family":"Karimi","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LinLin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Radiology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samer D.","family":"Tabbal","sequence":"additional","affiliation":[{"name":"Department of Neurology American University of Beirut Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan K.","family":"Loftin","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Moerlein","sequence":"additional","affiliation":[{"name":"Department of Radiology Washington University of Medicine St Louis MO"},{"name":"Department of Biochemistry and Molecular Biophysics Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel S.","family":"Perlmutter","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University of Medicine St Louis MO"},{"name":"Department of Radiology Washington University of Medicine St Louis MO"},{"name":"Department of Neurobiology Washington University of Medicine St Louis MO"},{"name":"Department of Occupational Therapy Washington University of Medicine St Louis MO"},{"name":"Department of Physical Therapy Washington University of Medicine St Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,9,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.07.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10609"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20737"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149403.14458.7F"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031439"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23798"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.10.1777"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600276"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05108.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.08.024"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.1.231"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199611000-00025"},{"key":"e_1_2_7_15_1","first-page":"1186","article-title":"Cocaine congeners as PET imaging probes for dopamine terminals","volume":"37","author":"Brownell A\u2010L","year":"1996","journal-title":"J Nucl Med"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.04.072"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20891"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.5.1432"},{"key":"e_1_2_7_19_1","first-page":"455","article-title":"Performance evaluation of the microPET focus: a third\u2010generation microPET scanner dedicated to animal imaging","volume":"46","author":"Tai Y\u2010C","year":"2005","journal-title":"J Nucl Med"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandc.2007.10.002"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2005.05.002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(00)00137-2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200004000-00002"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1983.1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.87"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.03.027"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971117)388:2<211::AID-CNE3>3.0.CO;2-4"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-13-04135.1996"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870100312"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199607000-00018"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199911)34:2<111::AID-SYN4>3.0.CO;2-0"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199708180-00017"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.10.090"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh198"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.6.6.823"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:28:3:209"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0956-9"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.23939","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.23939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T16:45:42Z","timestamp":1696610742000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.23939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,16]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1002\/ana.23939"],"URL":"https:\/\/doi.org\/10.1002\/ana.23939","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,16]]}}}