Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody
| Autor: | Melanie Hayden Gephart, Roan C Raymundo, Glenn Shields, Hannes Vogel, Monica Granucci, Nynke S. van den Berg, Marisa E. Hom, Eben L. Rosenthal, Wenying Kang, Gordon Li, Mark Roesner, Quan Zhou, Brock A. Martin, Grace Yi, Johana C. M. Vega Leonel, Natalie S. Lui, Stan van Keulen, Jacqueline Pei, Gerald A. Grant, Zachary P Hart, Naoki Nishio, Romain Cayrol, Myrthe Adriana Engelen, Yu-Jin Lee |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Fluorescence-lifetime imaging microscopy biology business.industry Receptor expression medicine.disease Head and neck squamous-cell carcinoma EGFR Antibody Surgery Glioma medicine biology.protein Adenocarcinoma Immunohistochemistry Epidermal growth factor receptor business |
| Popis: | BackgroundAs receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types is unknown. Near-infrared (NIR) labeled epidermal growth factor receptor (EGFR) antibody, panitumumab-IRDye800, was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework.MethodsThirty-one patients diagnosed with high-grade glioma (HGG, n=5, NCT03510208), head and neck squamous cell carcinoma (HNSCC, n=23, NCT02415881) or lung adenocarcinoma (LAC, n=3, NCT03582124) received systemic administration of 50 mg panitumumab-IRDye800 days prior to surgery. Intraoperative NIR laparoscopic or open-field images of the surgical field were acquired and tissue mimicking phantoms were constructed to identify optimal imaging conditions. Margin distance was correlated to fluorescence on resected specimen surface. Panitumumab-IRDye800 distribution was registered to histology in fixed tissue sections. Immunohistochemistry characterized EGFR expression.ResultsIntraoperative NIR imaging enhanced tumor contrast against surrounding healthy tissue by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Imaging quality was optimal at the lowest gain possible under ambient light. Ex vivo NIR fluorescence identified 78 – 97% of at-risk resection margins, with 72 – 92% sensitivity and 67 – 96% specificity for tumor in fixed tissue sections. Intratumoral panitumumab-IRDye800 concentration correlated with total tumoral EGFR expression (HGG > HNSCC > LAC) and delivery barrier. Cellular EGFR expression (80%) and tumor cell density (3000 cells/mm2) was highest in HGG.ConclusionsIn multiple tumor types, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment despite disparate tumor cell density and heterogeneous delivery of pantimumab-IRDye800.Translational relevanceAs receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types remains unexamined. Near-infrared labeled epidermal growth factor receptor (EGFR) antibody was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework. Targeted fluorescence imaging was performed in patients infused with a consistent dose of panitumumab-IRDye800 using the same fluorescence imaging devices. In high-grade glioma, head and neck squamous cell carcinoma and lung adenocarcinoma, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment. While total EGFR expression and delivery barrier corresponded to overall panitumumab-IRDye800 distribution in tissue, tumor depth and operating room lighting can have greater influence over the intraoperative fluorescence contrast at specific tissue surface locations of a certain patient. These factors can facilitate selecting appropriate molecular target and tumor qualities to streamline translation across institutions and regulatory approval of new imaging probes. |
| Databáze: | OpenAIRE |
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