{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:17:25Z","timestamp":1783372645547,"version":"3.54.6"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Post Covid National Network"},{"name":"Stichting Long COVID"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714 is a valuable tracer for studying (neuro)inflammation, with well-characterized tracer kinetics and an established imaging window. However, its clinical utility is restricted by the TSPO polymorphism (rs6971), which influences binding affinity in humans. The newly developed tracer [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 overcomes this limitation and has shown promising results in a preclinical rat model. To further assess its clinical potential, we compared [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 to [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714 for inflammation imaging in SARS-CoV-2-infected macaques in a longitudinal setting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      Dynamic positron emission tomography (PET) imaging was conducted in four healthy macaques to identify the optimal imaging window for [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814. Four additional macaques were infected with SARS-CoV-2 and monitored for 12 months using whole-body PET-computed tomography (CT) with both tracers. Baseline scans were compared to PET-CTs obtained at 4, 9 and 16 days and at 6 and 12 months post-infection, covering the head, thorax and abdomen. Tracer uptake was assessed in several organs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 showed higher lung uptake with minimal washout compared to [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714. Although lung lesions developed after infection, [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 did not demonstrate lesion-specific uptake, unlike [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714. In the brain, the tracers also displayed divergent uptake patterns despite comparable TSPO levels across animals and regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 exhibits a distinct whole-body distribution, particularly in the lungs and brain, in both na\u00efve and SARS-CoV-2-infected macaques compared with [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714, likely reflecting differences in tracer kinetics. Based on these data, [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-814 may not fully replace [\n                      <jats:sup>18<\/jats:sup>\n                      F]DPA-714 for lung and brain imaging, and further studies are required to evaluate its suitability in other anatomical regions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-026-02094-9","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T16:13:36Z","timestamp":1775060016000},"page":"502-512","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of [18F]DPA-814 with [18F]DPA-714 for TSPO Imaging in an Experimental Model"],"prefix":"10.1007","volume":"28","author":[{"given":"J.","family":"van der Bie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Verschoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Nutma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Middeldorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Beaino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kassiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Danon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A. M.","family":"Langermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. D.","family":"Windhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-6535","authenticated-orcid":false,"given":"M. A.","family":"Stammes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"2094_CR1","doi-asserted-by":"crossref","unstructured":"Uzuegbunam BC, Rummel C, Librizzi D, Culmsee C, Hooshyar Yousefi B et al (2023) Radiotracers for imaging of inflammatory biomarkers TSPO and COX-2 in the brain and in the periphery. Int J Mol Sci. 24(24)","DOI":"10.3390\/ijms242417419"},{"key":"2094_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-025-07109-1","author":"W Beaino","year":"2025","unstructured":"Beaino W, Jm Kooijman E, Werry EL, Vellinga RJ, den Van Hoek J, Sohler G et al (2025) Development and evaluation of [11C]DPA-813 and [18F]DPA-814: novel TSPO PET tracers insensitive to human single nucleotide polymorphism rs6971. Eur J Nucl Med Mol Imaging. https:\/\/doi.org\/10.1007\/s00259-025-07109-1","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"24","key":"2094_CR3","doi-asserted-by":"publisher","first-page":"17656","DOI":"10.1021\/acs.jmedchem.1c01571","volume":"64","author":"Z Chen","year":"2021","unstructured":"Chen Z, Haider A, Chen J, Xiao Z, Gobbi L, Honer M et al (2021) The repertoire of small-molecule PET probes for neuroinflammation imaging: challenges and opportunities beyond TSPO. J Med Chem 64(24):17656\u201389","journal-title":"J Med Chem"},{"issue":"5","key":"2094_CR4","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/jcbfm.2014.261","volume":"35","author":"SS Golla","year":"2015","unstructured":"Golla SS, Boellaard R, Oikonen V, Hoffmann A, van Berckel BN, Windhorst AD et al (2015) Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer\u2019s disease patients. J Cereb Blood Flow Metab 35(5):766\u2013772","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"2094_CR5","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1111\/ejn.15613","volume":"55","author":"D Gouilly","year":"2022","unstructured":"Gouilly D, Saint-Aubert L, Ribeiro MJ, Salabert AS, Tauber C, Peran P et al (2022) Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer\u2019s disease: An update. Eur J Neurosci 55(5):1322\u20131343","journal-title":"Eur J Neurosci"},{"issue":"1","key":"2094_CR6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12974-018-1352-9","volume":"15","author":"MHJ Hagens","year":"2018","unstructured":"Hagens MHJ, Golla SV, Wijburg MT, Yaqub M, Heijtel D, Steenwijk MD et al (2018) In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET. J Neuroinflammation 15(1):314","journal-title":"J Neuroinflammation"},{"issue":"1","key":"2094_CR7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12974-023-02857-z","volume":"20","author":"JM Nieuwland","year":"2023","unstructured":"Nieuwland JM, Nutma E, Philippens I, Boszormenyi KP, Remarque EJ, Bakker J et al (2023) Longitudinal positron emission tomography and postmortem analysis reveals widespread neuroinflammation in SARS-CoV-2 infected rhesus macaques. J Neuroinflammation 20(1):179","journal-title":"J Neuroinflammation"},{"key":"2094_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nucmedbio.2022.05.002","volume":"112\u2013113","author":"L Meijer","year":"2022","unstructured":"Meijer L, Boszormenyi KP, Bakker J, Koopman G, Mooij P, Verel D et al (2022) Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta). Nucl Med Biol 112\u2013113:1\u20138","journal-title":"Nucl Med Biol"},{"issue":"7","key":"2094_CR9","first-page":"1142","volume":"66","author":"X Palard-Novello","year":"2025","unstructured":"Palard-Novello X, Visser D, Yaqub M, van de Giessen E, den Hollander ME, Windhorst AD et al (2025) Whole-body [18F]DPA-714 kinetic assessment using PET\/CT scanner with long axial field of view. J Nucl Med 66(7):1142\u20131148","journal-title":"J Nucl Med"},{"key":"2094_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2025.123518","volume":"473","author":"D Boniek","year":"2025","unstructured":"Boniek D, Malamut C (2025) A mini-review: application of the radiopharmaceutical [18F]DPA-714 in neuroinflammation research in post-SARS-CoV-2 patients. J Neurol Sci 473:123518","journal-title":"J Neurol Sci"},{"key":"2094_CR11","unstructured":"WHO (2022) Post COVID-19 condition (Long COVID). Available from https:\/\/www.who.int\/europe\/news-room\/fact-sheets\/item\/post-covid-19-condition"},{"key":"2094_CR12","doi-asserted-by":"crossref","unstructured":"O'Mahony L, Buwalda T, Blair M, Forde B, Lunjani N, Ambikan A, et al (2022) Impact of Long COVID on health and quality of life. HRB Open Res 5:31","DOI":"10.12688\/hrbopenres.13516.1"},{"issue":"1","key":"2094_CR13","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 et al (2011) Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med 52(1):24\u201332","journal-title":"J Nucl Med"},{"issue":"1","key":"2094_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jcbfm.2011.147","volume":"32","author":"DR Owen","year":"2012","unstructured":"Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A et al (2012) An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 32(1):1\u20135","journal-title":"J Cereb Blood Flow Metab"},{"issue":"6","key":"2094_CR15","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/s41577-018-0005-7","volume":"18","author":"JD Estes","year":"2018","unstructured":"Estes JD, Wong SW, Brenchley JM (2018) Nonhuman primate models of human viral infections. Nat Rev Immunol 18(6):390\u2013404","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"2094_CR16","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1053\/j.semnuclmed.2023.03.001","volume":"53","author":"J Kleynhans","year":"2023","unstructured":"Kleynhans J, Sathekge MM, Ebenhan T (2023) Preclinical research highlighting contemporary targeting mechanisms of radiolabelled compounds for PET based infection imaging. Semin Nucl Med 53(5):630\u2013643","journal-title":"Semin Nucl Med"},{"key":"2094_CR17","doi-asserted-by":"crossref","unstructured":"Boszormenyi KP, Stammes MA, Fagrouch ZC, Kiemenyi-Kayere G, Niphuis H, Mortier D, et al (2021) The post-acute phase of SARS-CoV-2 infection in two Macaque species is associated with signs of ongoing virus replication and pathology in pulmonary andextrapulmonary tissues. Viruses 13(8)","DOI":"10.3390\/v13081673"},{"issue":"2","key":"2094_CR18","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.molmed.2021.12.001","volume":"28","author":"MA Stammes","year":"2022","unstructured":"Stammes MA, Lee JH, Meijer L, Naninck T, Doyle-Meyers LA, White AG et al (2022) Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates. Trends Mol Med 28(2):123\u201342","journal-title":"Trends Mol Med"},{"issue":"1","key":"2094_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21389-9","volume":"12","author":"FJ Salguero","year":"2021","unstructured":"Salguero FJ, White AD, Slack GS, Fotheringham SA, Bewley KR, Gooch KE et al (2021) Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19. Nat Commun 12(1):1260","journal-title":"Nat Commun"},{"issue":"2","key":"2094_CR20","doi-asserted-by":"publisher","DOI":"10.4110\/in.2021.21.e12","volume":"21","author":"MAB Casel","year":"2021","unstructured":"Casel MAB, Rollon RG, Choi YK (2021) Experimental animal models of coronavirus infections: strengths and limitations. Immune Netw 21(2):e12","journal-title":"Immune Netw"},{"key":"2094_CR21","doi-asserted-by":"publisher","first-page":"1319862","DOI":"10.3389\/fvets.2023.1319862","volume":"10","author":"A Maaskant","year":"2023","unstructured":"Maaskant A, Scarsi KK, Meijer L, Roubos S, Louwerse AL, Remarque EJ et al (2023) Long-acting reversible contraception with etonogestrel implants in female macaques (Macaca mulatta and Macaca fascicularis). Front Vet Sci 10:1319862","journal-title":"Front Vet Sci"},{"issue":"6","key":"2094_CR22","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1007\/s11307-025-02057-6","volume":"27","author":"MA Stammes","year":"2025","unstructured":"Stammes MA, Vierboom MPM, Sombroek CC, Bakker J, Meijer L, Vervenne RAW et al (2025) Comparative study of [18F]DPA714 and [18F]FDG PET tracers in an experimental model of pulmonary tuberculosis. Mol Imaging Biol 27(6):943\u201353","journal-title":"Mol Imaging Biol"},{"key":"2094_CR23","doi-asserted-by":"crossref","unstructured":"Stammes MA, Bakker J, Vervenne RAW, Zijlmans DGM, van Geest L, Vierboom MPM, et al (2021) Recommendations for standardizing Thorax PET-CT in non-human primates by recent experience from Macaque studies. Animals (Basel) 11(1)","DOI":"10.3390\/ani11010204"},{"issue":"6","key":"2094_CR24","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1177\/00236772211026562","volume":"55","author":"B Tolgyesi","year":"2021","unstructured":"Tolgyesi B, Bakker J, Nagy K, Meijer L, van Geest L, Stammes MA (2021) Refined acquisition of high-resolution chest CTs in macaques by free breathing. Lab Anim 55(6):551\u20139","journal-title":"Lab Anim"},{"key":"2094_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/v14040776","author":"I Philippens","year":"2022","unstructured":"Philippens I, Boszormenyi KP, Wubben JAM, Fagrouch ZC, van Driel N, Mayenburg AQ (2022) Brain inflammation and intracellular alpha-Synuclein aggregates in macaques after SARS-CoV-2 infection. Viruses. https:\/\/doi.org\/10.3390\/v14040776","journal-title":"Viruses"},{"issue":"4","key":"2094_CR26","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.nucmedbio.2011.10.012","volume":"39","author":"N Arlicot","year":"2012","unstructured":"Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL et al (2012) Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol 39(4):570\u20138","journal-title":"Nucl Med Biol"},{"issue":"11","key":"2094_CR27","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.2967\/jnumed.124.269297","volume":"66","author":"D Visser","year":"2025","unstructured":"Visser D, Golla SSV, Palard-Novello X, Verfaillie SCJ, Verveen A, Koch DW et al (2025) Varying levels of inflammatory activity in brain and body of patients with persistent fatigue and difficulty concentrating after COVID-19: a TSPO PET study. J Nucl Med 66(11):1787\u201394","journal-title":"J Nucl Med"},{"key":"2094_CR28","doi-asserted-by":"crossref","unstructured":"Moen JK, Baker CA, Iwasaki A (2025) Neuroimmune pathophysiology of long COVID. Psychiatry Clin Neurosci 79(9):514-530","DOI":"10.1111\/pcn.13855"}],"container-title":["Molecular Imaging and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-026-02094-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11307-026-02094-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-026-02094-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:10:05Z","timestamp":1783372205000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11307-026-02094-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2094"],"URL":"https:\/\/doi.org\/10.1007\/s11307-026-02094-9","relation":{},"ISSN":["1536-1632","1860-2002"],"issn-type":[{"value":"1536-1632","type":"print"},{"value":"1860-2002","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"24 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}