Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody
Authors: Zhou Quan , van den Berg Nynke S. , Kang Wenying , Pei Jacqueline , Nishio Naoki , van Keulen Stan , Engelen Myrthe A. , Lee Yu-Jin , Hom Marisa , Vega Leonel Johana C. M. , Hart Zachary , Vogel Hannes , Cayrol Romain , Martin Brock A. , Roesner Mark , Shields Glenn , Lui Natalie , Gephart Melanie Hayden , Raymundo Roan C. , Yi Grace , Granucci Monica , Grant Gerald A. , Li Gordon , Rosenthal Eben L. 
Published: October 2021

Background

As 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.

Methods

Thirty-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.

Results

Intraoperative 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.

Conclusions

In 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 relevance

As 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.