Pathogen-specific Actinium-225 and Lutetium-177 labeled antibodies, as well as unbound radionuclide treatment show antimicrobial potential on a biofilm-associated implant infection - initial in vivo experience

Pathogen-specific Actinium-225 and Lutetium-177 labeled antibodies, as well as unbound radionuclide treatment show antimicrobial potential on a biofilm-associated implant infection - initial in vivo experience | 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 Pathogen-specific Actinium-225 and Lutetium-177 labeled antibodies, as well as unbound radionuclide treatment show antimicrobial potential on a biofilm-associated implant infection - initial in vivo experience F. Ruben. H.A. Nurmohamed, Kevin J.H. Allen, Mackenzie E. Malo, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7240967/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first in vivo use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a Staphylococcus aureus biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. To assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and ex vivo gamma counting. Radioimmunotherapy using an antibody against wall teichoic acid with Actinium-225 and Lutetium-177 treatment achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerance with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. These results suggest that in vivo radiation therapy may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections. Health sciences/Diseases Health sciences/Medical research Biological sciences/Microbiology Antibacterial strategies Biofilm Antibodies Radioimmunotherapy Targeted radiation Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementfile225Ac177LuRITstudyNurmohamedetalScientificReports.docx Cite Share Download PDF Status: Posted 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-7240967","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":496287621,"identity":"4a756d86-0e83-42bc-97f0-4d63c1dfd866","order_by":0,"name":"F. Ruben. H.A. 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A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first \u003cem\u003ein vivo\u003c/em\u003e use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a \u003cem\u003eStaphylococcus aureus\u003c/em\u003e biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. To assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and \u003cem\u003eex vivo\u003c/em\u003e gamma counting. Radioimmunotherapy using an antibody against wall teichoic acid with Actinium-225 and Lutetium-177 treatment achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerance with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. These results suggest that \u003cem\u003ein vivo\u003c/em\u003e radiation therapy may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections.\u003c/p\u003e","manuscriptTitle":"Pathogen-specific Actinium-225 and Lutetium-177 labeled antibodies, as well as unbound radionuclide treatment show antimicrobial potential on a biofilm-associated implant infection - initial in vivo experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 19:50:09","doi":"10.21203/rs.3.rs-7240967/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"04b5ec1b-b285-462f-814c-8bbd779b7507","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52710169,"name":"Health sciences/Diseases"},{"id":52710170,"name":"Health sciences/Medical research"},{"id":52710171,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2025-09-03T16:38:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-07 19:50:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7240967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7240967","identity":"rs-7240967","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}