Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy

Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy Michelle James, Renesmee Kuo, Mackenzie Carlson, Samantha Reyes, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5897539/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Multiple sclerosis (MS) is a chronic neurodegenerative disease driven by immune cell infiltration into the central nervous system (CNS). Despite the critical role of immune cells in MS initiation and progression, current standard of care imaging techniques rely on structural lesion assessments, often resulting in misdiagnoses and inaccurate disease staging. Here we describe a novel dendrimer positron emission tomography (PET) tracer, 18 F-flurimedrimer ( 18 F-FMD), for non-invasive detection and tracking of activated myeloid cells–key immune players in MS. Using an experimental autoimmune encephalomyelitis (EAE) murine model of MS, we demonstrate the ability of 18 F-FMD to specifically detect these cells at both presymptomatic and symptomatic stages, with signal intensity correlating with disease severity. We illustrate that 18 F-FMD can also accurately monitor the immunomodulatory effects of Food and Drug Administration (FDA)-approved disease-modifying MS drug fingolimod (FTY720) and a novel CSF1R dendranib (H74DS3M8), both of which reduced immune cell activation and halted disease progression. These findings highlight the potential of 18 F-FMD PET for early MS diagnosis and as a generalizable approach for real-time monitoring of therapeutic responses across various mechanisms. Since we have translated 18 F-FMD for clinical imaging, it has the potential to revolutionize patient stratification in clinical trials and optimize treatments, making precision medicine a reality for MS patients. Health sciences/Neurology/Neurological disorders/Multiple sclerosis Health sciences/Biomarkers/Diagnostic markers Physical sciences/Chemistry/Organic chemistry Biological sciences/Immunology/Innate immune cells/Monocytes and macrophages/Microglial cells Health sciences/Medical research/Translational research Full Text Additional Declarations Yes there is potential Competing Interest. N.G.A, S.S.M., and J.L.C. are employed by Ashvattha Therapeutics during the completion of this work. All other authors have declared no conflicts of interest. Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5897539","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":411561734,"identity":"417409d5-4739-4f25-83df-2beca9a1825a","order_by":0,"name":"Michelle 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All other authors have declared no conflicts of interest.","formattedTitle":"Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5897539/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5897539/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Multiple sclerosis (MS) is a chronic neurodegenerative disease driven by immune cell infiltration into the central nervous system (CNS). Despite the critical role of immune cells in MS initiation and progression, current standard of care imaging techniques rely on structural lesion assessments, often resulting in misdiagnoses and inaccurate disease staging. Here we describe a novel dendrimer positron emission tomography (PET) tracer, \u003csup\u003e18\u003c/sup\u003eF-flurimedrimer (\u003csup\u003e18\u003c/sup\u003eF-FMD), for non-invasive detection and tracking of activated myeloid cells–key immune players in MS. Using an experimental autoimmune encephalomyelitis (EAE) murine model of MS, we demonstrate the ability of \u003csup\u003e18\u003c/sup\u003eF-FMD to specifically detect these cells at both presymptomatic and symptomatic stages, with signal intensity correlating with disease severity. We illustrate that \u003csup\u003e18\u003c/sup\u003eF-FMD can also accurately monitor the immunomodulatory effects of Food and Drug Administration (FDA)-approved disease-modifying MS drug fingolimod (FTY720) and a novel CSF1R dendranib (H74DS3M8), both of which reduced immune cell activation and halted disease progression. These findings highlight the potential of \u003csup\u003e18\u003c/sup\u003eF-FMD PET for early MS diagnosis and as a generalizable approach for real-time monitoring of therapeutic responses across various mechanisms. Since we have translated \u003csup\u003e18\u003c/sup\u003eF-FMD for clinical imaging, it has the potential to revolutionize patient stratification in clinical trials and optimize treatments, making precision medicine a reality for MS patients.","manuscriptTitle":"Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-06 03:54:23","doi":"10.21203/rs.3.rs-5897539/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c55959fb-8976-4373-94cc-cda45fe063fa","owner":[],"postedDate":"February 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":43884445,"name":"Health sciences/Neurology/Neurological disorders/Multiple sclerosis"},{"id":43884446,"name":"Health sciences/Biomarkers/Diagnostic markers"},{"id":43884447,"name":"Physical sciences/Chemistry/Organic chemistry"},{"id":43884448,"name":"Biological sciences/Immunology/Innate immune cells/Monocytes and macrophages/Microglial cells"},{"id":43884449,"name":"Health sciences/Medical research/Translational research"}],"tags":[],"updatedAt":"2026-02-03T08:10:37+00:00","versionOfRecord":{"articleIdentity":"rs-5897539","link":"https://doi.org/10.1038/s41467-025-67907-x","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2026-01-30 05:00:00","publishedOnDateReadable":"January 30th, 2026"},"versionCreatedAt":"2025-02-06 03:54:23","video":"","vorDoi":"10.1038/s41467-025-67907-x","vorDoiUrl":"https://doi.org/10.1038/s41467-025-67907-x","workflowStages":[]},"version":"v1","identity":"rs-5897539","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5897539","identity":"rs-5897539","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}