Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody

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.