{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:58:22Z","timestamp":1793869102361,"version":"4.6.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014438","name":"Business Finland","doi-asserted-by":"crossref","award":["632\/31\/2015"],"award-info":[{"award-number":["632\/31\/2015"]}],"id":[{"id":"10.13039\/501100014438","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Finnish Society of Nuclear Medicine","award":["na"],"award-info":[{"award-number":["na"]}]},{"DOI":"10.13039\/501100011797","name":"Turun Yliopistollinen Keskussairaala","doi-asserted-by":"crossref","award":["ERVA 13303"],"award-info":[{"award-number":["ERVA 13303"]}],"id":[{"id":"10.13039\/501100011797","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008659","name":"European Committee for Treatment and Research in Multiple Sclerosis","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/100008659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008320","name":"Suomen Aivos\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/501100008320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008413","name":"Instrumentariumin Tiedes\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/501100008413","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Folate receptor-\u03b2 (FR-\u03b2) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-\u03b2 expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) to study patterns of FR-\u03b2 expression and evaluated its potential as an in vivo imaging target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Focal EAE was induced in rats using heat-killed Bacillus Calmette-Gu\u00e9rin followed by activation with complete Freund\u2019s adjuvant supplemented with<jats:italic>Mycobacterium tuberculosis<\/jats:italic>. The rats were assessed with magnetic resonance imaging and positron emission tomography\/computed tomography (PET\/CT) at acute (14\u2009days) and chronic (90\u2009days) phases of inflammation. The animals were finally sacrificed for ex vivo autoradiography of their brains. PET studies were performed using FR-\u03b2-targeting aluminum [<jats:sup>18<\/jats:sup>F]fluoride-labeled 1,4,7-triazacyclononane-<jats:italic>1,4,7<\/jats:italic>-triacetic acid conjugated folate ([<jats:sup>18<\/jats:sup>F]AlF-NOTA-folate,<jats:sup>18<\/jats:sup>F-FOL) and 18\u2009kDa translocator protein (TSPO)-targeting<jats:italic>N<\/jats:italic>-acetyl-<jats:italic>N<\/jats:italic>-(2-[<jats:sup>11<\/jats:sup>C]methoxybenzyl)-2-phenoxy-5-pyridinamine (<jats:sup>11<\/jats:sup>C-PBR28). Post-mortem immunohistochemistry was performed using anti-FR-\u03b2, anti-cluster of differentiation 68 (anti-CD68), anti-inducible nitric oxide synthase (anti-iNOS), and anti-mannose receptor C-type 1 (anti-MRC-1) antibodies. The specificity of<jats:sup>18<\/jats:sup>F-FOL binding was verified using in vitro brain sections with folate glucosamine used as a blocking agent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunohistochemical evaluation of focal EAE lesions demonstrated anti-FR-\u03b2 positive cells at the lesion border in both acute and chronic phases of inflammation. We found that anti-FR-\u03b2 correlated with anti-CD68 and anti-MRC-1 immunohistochemistry; for MRC-1, the correlation was most prominent in the chronic phase of inflammation. Both<jats:sup>18<\/jats:sup>F-FOL and<jats:sup>11<\/jats:sup>C-PBR28 radiotracers bound to the EAE lesions. Autoradiography studies verified that this binding took place in areas of anti-FR-\u03b2 positivity. A blocking assay using folate glucosamine further verified the tracer\u2019s specificity. In the chronic phase of EAE, the lesion-to-background ratio of<jats:sup>18<\/jats:sup>F-FOL was significantly higher than that of<jats:sup>11<\/jats:sup>C-PBR28 (<jats:italic>P<\/jats:italic>\u2009=\u20090.016).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our EAE results imply that FR-\u03b2 may be a useful target for in vivo imaging of multiple sclerosis-related immunopathology. FR-\u03b2-targeted PET imaging with<jats:sup>18<\/jats:sup>F-FOL may facilitate the monitoring of lesion development and complement the information obtained from TSPO imaging by bringing more specificity to the PET imaging armamentarium for neuroinflammation.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-019-1612-3","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T15:03:27Z","timestamp":1575385407000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats"],"prefix":"10.1186","volume":"16","author":[{"given":"Petri","family":"Elo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Liljenb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semi","family":"Helin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Teuho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Koskensalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virva","family":"Saunavaara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Marjam\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa","family":"Oikonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni","family":"Virta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Jalkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Airas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-7977","authenticated-orcid":false,"given":"Anne","family":"Roivainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"key":"1612_CR1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/j.1750-3639.2007.00064.x","volume":"17","author":"H Lassmann","year":"2007","unstructured":"Lassmann H, Br\u00fcck W, Lucchinetti C. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210\u20138.","journal-title":"Brain Pathol"},{"key":"1612_CR2","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1212\/WNL.46.4.907","volume":"46","author":"FD Lublin","year":"1996","unstructured":"Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National multiple sclerosis society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology. 1996;46:907\u201311.","journal-title":"Neurology"},{"key":"1612_CR3","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1212\/WNL.0b013e3182635645","volume":"79","author":"M Politis","year":"2012","unstructured":"Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini P. Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology. 2012;79:523\u201330.","journal-title":"Neurology"},{"key":"1612_CR4","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1002\/ana.24791","volume":"80","author":"E Herranz","year":"2016","unstructured":"Herranz E, Giann\u00ec C, Louapre C, Treaba CA, Govindarajan ST, Ouellette R, Loggia ML, Sloane JA, Madigan N, Izquierdo-Garcia D, Ward N, Mangeat G, Granberg T, Klawiter EC, Catana C, Hooker JM, Taylor N, Ionete C, Kinkel RP, Mainero C. Neuroinflammatory component of gray matter pathology in multiple sclerosis. Ann Neurol. 2016;80:776\u201390.","journal-title":"Ann Neurol"},{"key":"1612_CR5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jns.2017.12.004","volume":"385","author":"T Bunai","year":"2018","unstructured":"Bunai T, Terada T, Kono S, Yokokura M, Yoshikawa E, Futatsubashi M, Miyajima H, Ouchi Y. Neuroinflammation following disease modifying therapy in multiple sclerosis: a pilot positron emission tomography study. J Neurol Sci. 2018;385:30\u20133.","journal-title":"J Neurol Sci"},{"key":"1612_CR6","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1093\/brain\/awp070","volume":"132","author":"JM Frischer","year":"2009","unstructured":"Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer H, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009;132:1175\u201389.","journal-title":"Brain"},{"key":"1612_CR7","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.tins.2010.01.002","volume":"33","author":"V Siffrin","year":"2010","unstructured":"Siffrin V, Vogt J, Radbruch H, Nitsch R, Zipp F. Multiple sclerosis \u2013 candidate mechanisms underlying CNS atrophy. Trends Neurosci. 2010;33:202\u201310.","journal-title":"Trends Neurosci"},{"key":"1612_CR8","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2967\/jnumed.114.149955","volume":"56","author":"L Airas","year":"2015","unstructured":"Airas L, Dickens AM, Elo P, Marjam\u00e4ki P, Johansson J, Eskola O, Jones P, Trigg W, Solin O, Haaparanta-Solin M, Anthony DC, Rinne J. In vivo PET imaging demonstrates diminished microglial activation after fingolimod treatment in an animal model of multiple sclerosis. J Nucl Med. 2015;56:305\u201310.","journal-title":"J Nucl Med"},{"key":"1612_CR9","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1038\/nn.3469","volume":"16","author":"VE Miron","year":"2013","unstructured":"Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, French-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16:1211\u20138.","journal-title":"Nat Neurosci"},{"key":"1612_CR10","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.pneurobio.2010.06.005","volume":"92","author":"E Mix","year":"2010","unstructured":"Mix E, Meyer-Rienecker H, Hartung HP, Zettl UK. Animal models of multiple sclerosis -potentials and limitations. Prog Neurobiol. 2010;92:386\u2013404.","journal-title":"Prog Neurobiol"},{"key":"1612_CR11","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1038\/nn.3168","volume":"15","author":"RM Ransohoff","year":"2012","unstructured":"Ransohoff RM. Animal models of multiple sclerosis: the good, the bad and the bottom line. Nat Neurosci. 2012;15:1074\u20137.","journal-title":"Nat Neurosci"},{"key":"1612_CR12","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/nbm.1404","volume":"22","author":"S Serres","year":"2009","unstructured":"Serres S, Anthony DC, Jiang Y, Campbell SJ, Broom KA, Khrapitchev A, Sibson NR. Comparison of MRI signatures in pattern I and II multiple sclerosis models. NMR Biomed. 2009;22:1014\u201324.","journal-title":"NMR Biomed"},{"key":"1612_CR13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s13244-011-0128-x","volume":"3","author":"ASC Ching","year":"2012","unstructured":"Ching ASC, Kuhnast B, Damont A, Roeda D, Tavitian B, Doll\u00e9 F. Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases. Insights Imaging. 2012;3:111\u20139.","journal-title":"Insights Imaging"},{"key":"1612_CR14","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11481-012-9397-5","volume":"8","author":"E Harberts","year":"2013","unstructured":"Harberts E, Datta D, Chen S, Wohler JE, Oh U, Jacobson S. Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients. J NeuroImmune Pharmacol. 2013;8:51\u20137.","journal-title":"J NeuroImmune Pharmacol"},{"key":"1612_CR15","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1177\/0883073809338063","volume":"24","author":"S Kannan","year":"2009","unstructured":"Kannan S, Balakrishnan B, Muzik O, Romero R, Chugani D. Positron emission tomography imaging of neuroinflammation. J Child Neurol. 2009;24:1190\u20139.","journal-title":"J Child Neurol"},{"key":"1612_CR16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.neulet.2006.09.093","volume":"411","author":"M Imaizumi","year":"2007","unstructured":"Imaizumi M, Kim HJ, Zoghbi SS, Briard E, Hong J, Musachio JL, Fujita M. PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat. Neurosci Lett. 2007;411:200\u20135.","journal-title":"Neurosci Lett"},{"key":"1612_CR17","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1016\/j.neuroimage.2009.11.056","volume":"49","author":"WC Kreisl","year":"2010","unstructured":"Kreisl WC, Fujita M, Fujimura Y, Kimura N, Jenko KJ, Kannan P, Jacobson S. Comparison of [11C]-(R)-PK 11195 and [11C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: implications for positron emission tomographic imaging of this inflammation biomarker. Neuroimage. 2010;49:2924\u201332.","journal-title":"Neuroimage"},{"key":"1612_CR18","doi-asserted-by":"publisher","first-page":"24","DOI":"10.2967\/jnumed.110.079459","volume":"52","author":"DR Owen","year":"2011","unstructured":"Owen DR, Gunn RN, Rabiner EA, Bennacef I, Fujita M, Kreisl WC, Innis RB, Pike VW, Reynolds R, Matthews PM. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med. 2011;52:24\u201332.","journal-title":"J Nucl Med"},{"key":"1612_CR19","doi-asserted-by":"publisher","first-page":"607","DOI":"10.3390\/molecules23030607","volume":"23","author":"B Janssen","year":"2018","unstructured":"Janssen B, Vugts DJ, Windhorst AD, Mach RH. PET imaging of microglial activation-beyond targeting TSPO. Molecules. 2018;23:607.","journal-title":"Molecules"},{"key":"1612_CR20","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/j.1468-1331.2010.03154.x","volume":"18","author":"L Kiferle","year":"2011","unstructured":"Kiferle L, Politis M, Muraro PA, Piccini P. Positron emission tomography imaging in multiple sclerosis\u2013current status and future applications. Eur J Neurol. 2011;18:226\u201331.","journal-title":"Eur J Neurol"},{"key":"1612_CR21","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1002\/jps.20457","volume":"94","author":"AR Hilgenbrink","year":"2005","unstructured":"Hilgenbrink AR, Low PS. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005;94:2135\u201346.","journal-title":"J Pharm Sci"},{"key":"1612_CR22","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/art.10405","volume":"46","author":"MJ Turk","year":"2002","unstructured":"Turk MJ, Breur GJ, Widmer WR, Paulos CM, Xu LC, Grote LA, Low PS. Folate-targeted imaging of activated macrophages in rats with adjuvant-induced arthritis. Arthritis Rheum. 2002;46:1947\u201355.","journal-title":"Arthritis Rheum"},{"key":"1612_CR23","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1021\/ar7000815","volume":"41","author":"PS Low","year":"2007","unstructured":"Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2007;41:120\u20139.","journal-title":"Acc Chem Res"},{"key":"1612_CR24","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1021\/acs.molpharmaceut.5b00989","volume":"13","author":"Q Chen","year":"2016","unstructured":"Chen Q, Meng X, McQuade P, Rubins D, Lin S, Zeng Z, Low PS. Synthesis and preclinical evaluation of Folate-NOTA-Al18F for PET imaging of folate-receptor-positive tumors. Mol Pharm. 2016;13:1520\u20137.","journal-title":"Mol Pharm"},{"key":"1612_CR25","first-page":"1","volume":"9720","author":"JMU Silvola","year":"2018","unstructured":"Silvola JMU, Li XG, Virta J, Marjam\u00e4ki P, Liljenb\u00e4ck H, Hyt\u00f6nen JP, Tarkia M, Saunavaara V, Hurme S, Palani S, Hakovirta H, Yl\u00e4-Herttuala S, Saukko P, Chen Q, Low PS, Knuuti J, Saraste A, Roivainen A. Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography. Sci Rep. 2018;9720:1\u201315.","journal-title":"Sci Rep"},{"key":"1612_CR26","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1177\/1352458510379243","volume":"17","author":"J Mikita","year":"2011","unstructured":"Mikita J, Dubourdieu-Cassagno N, Deloire MS, Vekris A, Biran M, Raffard G, Brochet B, Canron MH, Franconi JM, Boiziau C, Petry KG. Altered M1\/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult Scler. 2011;17:2\u201315.","journal-title":"Mult Scler"},{"key":"1612_CR27","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00401-014-1310-2","volume":"128","author":"JF Bogie","year":"2014","unstructured":"Bogie JF, Stinissen P, Hendriks JJ. Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathol. 2014;128:191\u2013213.","journal-title":"Acta Neuropathol"},{"key":"1612_CR28","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.2147\/NDT.S140634","volume":"13","author":"C Luo","year":"2017","unstructured":"Luo C, Jian C, Liao Y, Huang Q, Wu Y, Liu X, Donghua Z, Yuan W. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat. 2017;13:1661\u20137.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"1612_CR29","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/0306-4522(94)00448-E","volume":"64","author":"MK Matyszak","year":"1995","unstructured":"Matyszak MK, Perry VH. Demyelination in the central nervous system following a delayed-type hypersensitivity response to bacillus Calmette-Guerin. Neuroscience. 1995;64:967\u201377.","journal-title":"Neuroscience"},{"key":"1612_CR30","doi-asserted-by":"publisher","first-page":"991","DOI":"10.2967\/jnumed.108.060418","volume":"50","author":"WJ McBride","year":"2009","unstructured":"McBride WJ, Sharkey RM, Karacay H, D'Souza CA, Rossi EA, Laverman P, Goldenberg DM. A novel method of 18F radiolabeling for PET. J Nucl Med. 2009;50:991\u20138.","journal-title":"J Nucl Med"},{"key":"1612_CR31","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/nprot.2013.170","volume":"9","author":"XG Li","year":"2014","unstructured":"Li XG, Helariutta K, Roivainen A, Jalkanen S, Knuuti J, Airaksinen AJ. Using 5-deoxy-5-[18F]fluororibose to glycosylate peptides for positron emission tomography. Nat Protoc. 2014;9:138\u201345.","journal-title":"Nat Protoc"},{"key":"1612_CR32","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1007\/s00259-019-04403-7","volume":"46","author":"J Tuisku","year":"2019","unstructured":"Tuisku J, Plaven-Sigray P, Gaiser EC, Airas L, Al-Abdulrasul H, Bruck A, Carson RE, Chen MK, Cosgrove KP, Ekblad L, Esterlis I, Farde L, Forsberg A, Halldin C, Helin S, Kosek E, Lekander M, Lindgren N, Marjam\u00e4ki P, Rissanen E, Suckdorff M, Varrone A, HRRT [11C ]PBR28 study group, Collste K, Gallezot JD, Hillmer, Rinne J, Matuskey D, Cervenka S. Effects of age, BMI and sex on the glial cell marker TSPO \u2014 a multicentre [11C]PBR28 HRRT PET study. Eur J Nucl Med Mol Imaging. 2019;46:2329\u201338.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"1612_CR33","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.2967\/jnumed.111.099382","volume":"53","author":"AL Goertzen","year":"2012","unstructured":"Goertzen AL, Bao Q, Bergeron M, Blankemeyer E, Blinder S, Canadas M, Chatziioannou AF, Dinelle K, Elhami E, Jans H-S, Lage E, Lecomte R, Sossi V, Surti S, Tai YC, Vaquero JJ, Vicente E, Williams DA, Laforest R. NEMA NU 4-2008 comparison of preclinical PET imaging systems. J Nucl Med. 2012;53:1300\u20139.","journal-title":"J Nucl Med"},{"key":"1612_CR34","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/ajcp\/88.5.589","volume":"88","author":"LM Muramoto","year":"1987","unstructured":"Muramoto LM, Kadin ME. Improved detection of lymphoid cell surface antigens in tissues fixed in periodate-lysine-paraformaldehyde (PLP). Am J Pathol. 1987;88:589\u201395.","journal-title":"Am J Pathol"},{"key":"1612_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar3312","volume":"13","author":"Y Feng","year":"2011","unstructured":"Feng Y, Shen J, Streaker ED, Lockwood M, Zhu Z, Low PS, Dimitrov DS. A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibody-dependent cell-mediated cytotoxicity. Arthritis Res Ther. 2011;13:1\u201312.","journal-title":"Arthritis Res Ther"},{"key":"1612_CR36","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.clim.2013.10.010","volume":"150","author":"Y Lu","year":"2014","unstructured":"Lu Y, Wollak KN, Cross VA, Westrick E, Wheeler LW, Stinnette TW, Vaughn JF, Hahn SJ, Xu LC, Vlahov IR, Leamon CP. Folate receptor-targeted aminopterin therapy is highly effective and specific in experimental models of autoimmune uveitis and autoimmune encephalomyelitis. Clin Immunol. 2014;150:64\u201377.","journal-title":"Clin Immunol"},{"key":"1612_CR37","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1002\/art.22082","volume":"54","author":"T Nagai","year":"2006","unstructured":"Nagai T, Tanaka M, Tsuneyoshi Y, Matsushita K, Sunahara N, Matsuda T, Yoshida H, Komiya S, Onda M, Matsuyama T. In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells. Arthritis Rheum. 2006;54:3126\u201334.","journal-title":"Arthritis Rheum"},{"key":"1612_CR38","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3109\/03009742.2011.605391","volume":"41","author":"Y Tsuneyoshi","year":"2012","unstructured":"Tsuneyoshi Y, Tanaka M, Nagai T, Sunahara N, Matsuda T, Sonoda T, Ijiri K, Komiya S, Matsuyama T. Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1\/M2 expression profiles. Scand J Rheumatol. 2012;41:132\u201340.","journal-title":"Scand J Rheumatol"},{"key":"1612_CR39","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.neuropharm.2013.12.022","volume":"79","author":"DC Anthony","year":"2014","unstructured":"Anthony DC, Sibson NR, Losey P, Meier DP, Leppert D. Investigation of immune and CNS-mediated effects of fingolimod in the focal delayed-type hypersensitivity multiple sclerosis model. Neuropharmacology. 2014;79:541\u20133.","journal-title":"Neuropharmacology"},{"key":"1612_CR40","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","volume":"338","author":"N Parker","year":"2005","unstructured":"Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005;338:284\u201393.","journal-title":"Anal Biochem"},{"key":"1612_CR41","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.2967\/jnumed.114.143180","volume":"55","author":"NA Jager","year":"2014","unstructured":"Jager NA, Westra J, Golestani R, van Dam GM, Low PS, Tio RA, Slart RHJA, Boersma HH, Bijl M, Zeebergts CJ. Folate receptor-beta imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque. J Nucl Med. 2014;55:1945\u201351.","journal-title":"J Nucl Med"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1612-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-019-1612-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1612-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T02:37:15Z","timestamp":1722134235000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-019-1612-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1612"],"URL":"https:\/\/doi.org\/10.1186\/s12974-019-1612-3","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"21 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All study protocols and procedures were reviewed and approved by the national Animal Experiment Board of Finland and the Regional State Administrative Agency for Southern Finland (license number ESAVI\/3046\/04.10.07\/2014) and were conducted in accordance with the relevant European Union directive.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"252"}}