Tumor-specific intraoperative detection of pancreatic ductal adenocarcinoma using multimodal molecular imaging

Abstract

Background: Two major predictors of long term survival of pancreatic cancer are the ability to resect tumor with cancer free margins and absence of systemic metastases. Unfortunately, margin positive resections are a frequent phenomenon as is the emergence of distant metastases soon after surgery. The use of tumor targeted molecular imaging has the potential to provide crucial information to surgeon, both in the form of fluorescent and photoacoustic imaging. Here, we report the use of Cetuximab-IRDye800, a near-infrared fluorescent agent, that binds to EGFR for intraoperative detection of pancreatic cancer. Methods: A dose escalation study of Cetuximab conjugated to IRDye800 was performed in patients (n=7) undergoing surgical resection of pancreatic cancer. Safety and pharmacokinetic data were obtained up to 30 days after infusion. Multi-instrument fluorescence and photoacoustic imaging was performed both in the operating room and ex vivo. Results: There were no grade 2 or higher adverse events attributable to the intravenous injection of cetuximab-IRDye800. Fluorescence imaging successfully differentiated tumor and positive lymph nodes from normal tissue during resection with average tumor-to-background ratio of 8.7. Ex vivo fluorescence, photoacoustic and pathologic examination confirmed correlation between tumor and fluorescent and photoacoustic signal. Conclusion: This study demonstrates safety and feasibility of tumor-specific Cetuximab-IRDye800 for multimodal molecular intraoperative imaging of pancreatic cancer.