A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent

Pieter Jan Steinkamp, Floris Jan Voskuil, Bert van der Vegt, Jan Johannes Doff, Kees Pieter Schepman, Sebastiaan Antonius Hendrik Johannes de Visscher, Wendy Kelder, Yalia Jayalakshmi, Jinming Gao, Baran Devrim Sumer, Gooitzen Michell van Dam, Max Johannes Hendrikus Witjes

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose: Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have to rely on visual and tactile information. Fluorescence-guided surgery using tumor-specific imaging agents can assist in clinical decision-making. However, a standardized imaging methodology is lacking. In this study, we determined whether a standardized, specimen-driven, fluorescence imaging framework using ONM-100 could assist in clinical decision-making during surgery. Procedures: Thirteen patients with histologically proven HNSCC were included in this clinical study and received ONM-100 24 ± 8 h before surgery. Fluorescence images of the excised surgical specimen and of the surgical cavity were analyzed. A fluorescent lesion with a tumor-to-background ratio (TBR) > 1.5 was considered fluorescence-positive and correlated to standard of care (SOC) histopathology. Results: All six tumor-positive surgical margins were detected immediately after excision using fluorescence-guided intra-operative imaging. Postoperative analysis showed a median TBR (±IQR) of the fluorescent lesions on the resection margin of 3.36 ± 1.62. Three fluorescence-positive lesions in the surgical cavity were biopsied and showed occult carcinoma and severe dysplasia, and a false-positive fluorescence lesion. Conclusion: Our specimen-driven fluorescence framework using a novel, pH-activatable, fluorescent imaging agent could assist in reliable and real-time adequate clinical decision-making showing that a fluorescent lesion on the surgical specimen with a TBR of 1.5 is correlated to a tumor-positive resection margin. The binary mechanism of ONM-100 allows for a sharp tumor delineation in all patients, giving the surgeon a clinical tool for real-time margin assessment, with a high sensitivity.

Original languageEnglish (US)
Pages (from-to)809-817
Number of pages9
JournalMolecular Imaging and Biology
Issue number6
StatePublished - Dec 2021


  • Fluorescence-guided surgery
  • Margin assessment
  • Standardization
  • Tumor type-agnostic imaging
  • pH activation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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