B.E. Zweedijk, L.J. Lauwerends, H.A. Galema, D. J. Robinson, H.S.De Bruijn, H. Abbasi, T. L. March, A. R. P. M. Valentijn, M. Pool, H. Mast, B. P. Jonker, J. A. U. Hardillo, D. Monserez, A. Sewnaik, S. Koljenović, C. Verhoef, R. J. Baatenburg de Jong, J.V. Frangioni, S.A. Koppes, D. E. Hilling, A.L. Vahrmeijer, S. Keereweer
In oral squamous cell carcinoma (OSCC) surgery, inadequate tumor margins are reported in up to 85% of cases, adversely affecting outcomes. In this prospective, single-center study (n = 31; 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 mg/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 mg/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.