Abstract
Background: Pancreatic cancer (PC) has a very poor prognosis. Surgery is the standard treatment for resectable PC but the accurate intraoperative identification and resection of intrapancreatic tumors remain challenging and tumor residuals frequently cause local recurrence. We have developed a novel open-type positron emission tomography (PET) system (called “OpenPET”) that enables high-resolution PET-guided surgery in real-time. Furthermore, we have demonstrated that OpenPET-guided surgery with ip-administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab can image and remove primary small (< 1 cm) resectable PC tumors in an orthotopic xenograft mouse model. Here, we further investigated the usefulness of OpenPET-guided surgery for the intraoperative identification and resection of not only primary but also unexpected residual intrapancreatic tumors using an orthotopic xenograft mouse model with large (> 1 cm) resectable PC and examined its survival benefit over conventional surgery.Methods: To establish the model, human PC xPA-1-DC cells expressing red fluorescent protein (RFP) were slowly inoculated into the mouse pancreas. To investigate its usefulness, OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). The survival rate after OpenPET-guided surgery was compared to that after control operations. Results: The intraoperative OpenPET guidance enabled the detection and resection of both primary and small residual tumors. In this study, 10 residual tumor specimens were intraoperatively isolated with OpenPET guidance (n=7 mice); three and seven tumors were 5–10 mm and 3–5 mm in diameter, respectively. In all isolated specimens, tumor RFP signals were detected. By contrast, no tumor tissue was resected in control group because in this model, the locations and boundaries of primary tumors within the pancreas were not clearly detectable by the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group.Conclusions: OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled the intraoperative identification and resection of intrapancreatic primary and residual tumors in vivo. This technology could be useful to prevent tumor residuals during surgery and improve PC survival.
Evaluation of 89Zr-Labeled Human Anti-CD147 Monoclonal Antibody as a Positron Emission Tomography Probe in a Mouse Model of Pancreatic Cancer
