{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:03:11Z","timestamp":1787972591845,"version":"build-2784847793"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005609","name":"University of Turku","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005609","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer\u2019s ability to target the macrophage mannose receptor CD206.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>First, the uptake of intravenously (i.v.) administered Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM was compared between wild-type (WT) and CD206<jats:sup>\u2212\/\u2212<\/jats:sup> knockout (KO) mice. C57BL\/6N mice were injected with complete Freund\u2019s adjuvant (CFA) in the left hind leg and the uptake of Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14\u00a0days after CFA induction of inflammation. Healthy C57BL\/6N mice were studied as controls. Mice underwent PET\/CT on consecutive days with [<jats:sup>18<\/jats:sup>F]FDG, i.v. Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM, and i.d. Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM. After the last imaging, Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with WT mice, the uptake of Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM was significantly lower in several CD206<jats:sup>\u2212\/\u2212<\/jats:sup> KO mice tissues, including liver (SUV 8.21\u2009\u00b1\u20092.51 <jats:italic>vs.<\/jats:italic> 1.06\u2009\u00b1\u20090.16, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and bone marrow (SUV 1.63\u2009\u00b1\u20090.37 <jats:italic>vs.<\/jats:italic> 0.22\u2009\u00b1\u20090.05, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). The uptake of i.v. injected Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM was significantly higher in inflamed ankle joint (SUV 0.48\u2009\u00b1\u20090.13 <jats:italic>vs.<\/jats:italic> 0.18\u2009\u00b1\u20090.05, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) and inflamed foot pad skin (SUV 0.41\u2009\u00b1\u20090.10 <jats:italic>vs.<\/jats:italic> 0.04\u2009\u00b1\u20090.01, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) than in the corresponding tissues in healthy mice. The i.d.-injected Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM revealed differences between CFA-induced lymph node activation and lymph nodes in healthy mice. Ex vivo \u03b3-counting, autoradiography, and immunohistochemistry supported the results, and a decrease of\u2009~\u200980% in the binding of Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM in the displacement study with excess NOTA-D10CM confirmed that tracer binding was specific. At 60\u00a0min after i.v. injection, an average 96.70% of plasma radioactivity was derived from intact Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM, indicating good in vivo stability. The uptake of Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM into inflamed tissues was positively associated with the area percentage of CD206-positive staining.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The uptake of mannosylated dextran derivative Al[<jats:sup>18<\/jats:sup>F]F-NOTA-D10CM correlated with CD206 expression and the tracer appears promising for inflammation imaging.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00259-024-06686-x","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T05:57:41Z","timestamp":1711519061000},"page":"2216-2228","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice"],"prefix":"10.1007","volume":"51","author":[{"given":"Putri","family":"Andriana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Fair-M\u00e4kel\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Liljenb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salli","family":"K\u00e4rn\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Makrypidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Rajander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Pirmettis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Jalkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Saraste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Salmi","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":[[2024,3,27]]},"reference":[{"key":"6686_CR1","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1189\/jlb.0512231","volume":"92","author":"L Martinez-Pomares","year":"2012","unstructured":"Martinez-Pomares L. 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The remaining authors have no conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}