Safety and tumor specificity of cetuximab-IRDye800 for surgical navigation in head and neck cancer

Eben L. Rosenthal, Jason M. Warram, Esther De Boer, Thomas K. Chung, Melissa L. Korb, Margie Brandwein-Gensler, Theresa V. Strong, Cecelia E. Schmalbach, Anthony B. Morlandt, Garima Agarwal, Yolanda E. Hartman, William R. Carroll, Joshua S. Richman, Lisa K. Clemons, Lisle M. Nabell, Kurt R. Zinn

Research output: Contribution to journalArticlepeer-review

255 Scopus citations

Abstract

Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer. Experimental Design: A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results: There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-tobackground ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels. Conclusions: We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology.

Original languageEnglish (US)
Pages (from-to)3658-3666
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number16
DOIs
StatePublished - Aug 15 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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