Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging
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Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.
A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.
Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.
The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.
The authors acknowledge support from Stanford Cancer Institute Translational Research Grant, and Intuitive Surgical Clinical Robotics Research Grant. Tummers WS contribution to this work was supported in part by Michaël-van Vloten Fonds, Lisa Waller Hayes Foundation, Jo Kolk Studiefonds, McKinsey Grant, and Ketel1 Studiefonds. Huland DM contribution to this work was supported in part by NCI training grant: T32 CA118681.
ELR, GAP, SSG, BAB, ALV, RJS and WST designed the research; WST, SEM, NT, AG, IS, DMH, SH, SRK, AH, RE, TAL, GAF, and GAP performed the research; and WST, SEM, and ELR analyzed data and wrote the paper.
The authors declare no potential conflicts of interest.
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