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Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer



To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW.


Patients (n = 24) received either 0.5 or 1.0 mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50 mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging.


A total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate–strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2 = 0.42) and for dose/weight (mg/kg) (R2 = 0.54). Results indicated that the optimal MFI was at approximately 50 mg for fixed dose and 0.75 mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2 days (vs. 3 days or more, p < 0.05).


Antibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50 mg is an appropriate diagnostic dose for successful surgical fluorescence imaging.

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This work was supported in part by the Stanford Comprehensive Cancer Center, the Stanford University School of Medicine Medical Scholars Program, the Netherlands Organization for Scientific Research (Rubicon; 019.171LW.022), the National Institutes of Health and the National Cancer Institute (R01CA190306), and the Stanford Molecular Imaging Scholars (SMIS) program (NIT T32CA118681). Institutional equipment loans were received from Novadaq, SurgVision, and LI-COR Biosciences.

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Correspondence to Eben L. Rosenthal.

Ethics declarations

The study protocol was approved by the Stanford University Institutional Review Board and the FDA (NCT02415881). Informed consent was obtained from all individual participants included in the study. The study was performed in accordance with the Helsinki Declaration of 1975 and its amendments, FDA’s ICH-GCP guidelines, and the laws and regulations of the USA.

Conflict of Interest

Eben Rosenthal is a consultant for LICOR Biosciences that manufactures IRDye800 and has equipment loans from this company.

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Nishio, N., van den Berg, N.S., van Keulen, S. et al. Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. Mol Imaging Biol 22, 156–164 (2020). https://doi.org/10.1007/s11307-019-01358-x

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Key words

  • Fluorescence
  • Near-infrared imaging
  • Head and neck cancer
  • Optimal dosing strategy
  • Panitumumab
  • Image-guided surgery
  • EGFR
  • IRDye800CW