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Early, specific, and preferably non-invasive diagnostic tools, such as bacteria-targeting imaging agents, are essential for optimal treatment, since current approaches, including white blood cell scintigraphy and [\u00b9\u2078F]FDG-PET, are accurate, but may lack specificity. Vancomycin, an antibiotic targeting Gram-positive bacteria, has been successfully applied as a molecular scaffold for bacteria-specific tracer development. This study evaluated two novel vancomycin-based PET tracers, [\u00b9\u2078F]BODIPY-FL-vancomycin and [\u00b9\u2078F]VE1-PQ-vancomycin, along with the fluorescent tracer vancomycin-IRDye800CW, for diagnosing biofilm-associated orthopaedic implant infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a preclinical in vivo model of orthopaedic implant infection, where C57BL\/6 mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200972) received stainless-steel Kirschner (K)-wire implants in the distal femur, which were inoculated with bioluminescent\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      or\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      bacteria, or with PBS (sterile control). At days 13\u201314 post-implant infection, animals were injected with one of the vancomycin tracers or [\u00b9\u2078F]FDG (benchmark control) and underwent PET\/CT or fluorescence imaging. Tracer accumulation at the infection site was quantified, followed by biodistribution analysis and bacterial load assessment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both vancomycin-based PET tracers showed significantly higher uptake in\n                      <jats:italic>S. aureus<\/jats:italic>\n                      -infected legs compared to sterile controls. The differences in binding between\n                      <jats:italic>S. aureus<\/jats:italic>\n                      or\n                      <jats:italic>E. coli<\/jats:italic>\n                      were less distinct. In this model, [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG did not distinguish K-wire infection from sterile controls. Vancomycin-IRDye800CW accumulated specifically at\n                      <jats:italic>S. aureus<\/jats:italic>\n                      infection sites, but not at\n                      <jats:italic>E. coli<\/jats:italic>\n                      infection sites or sterile controls, indicating accurate bacteria-targeted imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Vancomycin-based PET and optical tracers differentiated bacterial infection from the sterile K-wire controls in a murine model. Optical imaging distinguished Gram-positive from Gram-negative bacterial infection, whereas PET tracers did not. These preclinical findings support further investigation of vancomycin-based tracers for non-invasive imaging of prosthetic joint and fracture-related infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07997-x","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:38:03Z","timestamp":1781833083000},"page":"6098-6110","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In vivo bacteria-targeted imaging with vancomycin-based positron emission tomography and optical tracers in an orthopaedic trauma implant infection model"],"prefix":"10.1007","volume":"53","author":[{"given":"Gerbren B.","family":"Spoelstra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisanne M.","family":"Braams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank F. 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J Orthop Res. 2012;30(3):335\u201340. https:\/\/doi.org\/10.1002\/jor.21519.","journal-title":"J Orthop Res"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07997-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-07997-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07997-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:10:23Z","timestamp":1785521423000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-07997-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["7997"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-07997-x","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]},"assertion":[{"value":"11 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experiments were conducted in accordance with Dutch and EU laws and were performed in the Central Animal Facility of the University of Groningen (Centrale Dienst Dierproeven). Experimental protocols were approved by the National Committee on Animal Experiments of The Netherlands (Centrale Commissie Dierproeven, Den Haag) and the Institutional Animal Care and Use Committee of the University of Groningen (Instantie voor Dierproeven (IvD), CCD license number: AVD10500202114768. IvD licence number: 2114768-01-004).","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have agreed with publication of this manuscript.","order":3,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no personal competing interests. However, it should be noticed that funding was in part provided by Stryker European Operations Ltd., and that the project was supported by a user committee of Stryker European Operations Ltd. and Siemens AG. Kevin Francis is a consultant for Bruker Corporation and Philip H. Elsinga is an editor of the European Journal of Nuclear Medicine and Molecular Imaging.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}