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03.05.2019 | Research Article

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

verfasst von: Naoki Nishio, Nynke S. van den Berg, Stan van Keulen, Brock A. Martin, Shayan Fakurnejad, Quan Zhou, Guolan Lu, Stefania U. Chirita, Michael J. Kaplan, Vasu Divi, Alexander D. Colevas, Eben L. Rosenthal

Erschienen in: Molecular Imaging and Biology | Ausgabe 1/2020

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Abstract

Purpose

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.

Procedures

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.

Results

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).

Conclusions

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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Titel: Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer
verfasst von: Naoki Nishio
Nynke S. van den Berg
Stan van Keulen
Brock A. Martin
Shayan Fakurnejad
Quan Zhou
Guolan Lu
Stefania U. Chirita
Michael J. Kaplan
Vasu Divi
Alexander D. Colevas
Eben L. Rosenthal
Publikationsdatum: 03.05.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 1/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01358-x

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