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In this prospective, single-center study (n\u2009=\u200931; NCT04191460), we evaluated the safety and imaging feasibility of cRGD-ZW800-1, a near-infrared fluorescent integrin-targeted tracer. The secondary objective was to determine whether intraoperative fluorescence imaging could identify inadequate resection margins and inform surgical decision-making. Patients received 0.01, 0.025, or 0.05\u2009mg\/kg cRGD-ZW800-1, and tracer uptake was quantified using in vivo multi-diameter single-fiber reflectance and single-fiber fluorescence spectroscopy to optimize dosing and timing. All doses were well tolerated, achieving tumor-to-background ratios exceeding 4.5, with optimal performance at 0.025\u2009mg\/kg. Fluorescence imaging detected all 23 inadequate margins, including nine undetected by conventional assessment (sensitivity 100% versus 70%), altered surgical plans in five cases, and avoided adjuvant radiotherapy in three cases. These findings demonstrate that cRGD-ZW800-1 is safe, tumor-specific, and facilitates intraoperative margin assessment in OSCC.<\/jats:p>","DOI":"10.1038\/s41467-026-73554-7","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T22:04:48Z","timestamp":1779487488000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Near-infrared fluorescence imaging-guided surgery using cRGD-ZW800 to improve surgical resection margins in oral cancer: a phase I\/II feasibility trial"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9256-6770","authenticated-orcid":false,"given":"B. E.","family":"Zweedijk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. J.","family":"Lauwerends","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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