Near-infrared fluorescence imaging-guided surgery using cRGD-ZW800 to improve surgical resection margins in oral cancer: a phase I/II feasibility trial
- 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. Koljenovic
- C. Verhoef
- R. J. Baatenburg de Jong
- J. V. Frangioni
- S. A. Koppes
- D. E. Hilling
- A. L. Vahrmeijer
- S. Keereweer
2026-05-22
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.