Theranostics 2018; 8(9):2488-2495. doi:10.7150/thno.24487
Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers
1. Stanford University School of Medicine
2. Department of Otolaryngology, Stanford University
3. Department of Surgery, University Medical Center Groningen, University of Groningen
4. Department of Medicine, Division of Oncology, Stanford University
5. Department of Otolaryngology, University of Alabama at Birmingham
Gao RW, Teraphongphom N, de Boer E, Berg NSvd, Divi V, Kaplan MJ, Oberhelman NJ, Hong SS, Capes E, Colevas AD, Warram JM, Rosenthal EL. Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics 2018; 8(9):2488-2495. doi:10.7150/thno.24487. Available from https://www.thno.org/v08p2488.htm
Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging.
Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion.
Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8).
Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.