Highly Sensitive Detection of Occult Pancreatic Cancer Using Intraoperative Molecular Imaging

Abstract public domain (NIH RePORTER)

PROJECT SUMMARY/ABSTRACT The failure of surgery to provide a long-disease free survival interval to patients with resected pancreatic cancer is related to the inability to recognize occult tumor foci at metastatic or locoregional sites. For surgery to be effective, there is a critical need for real-time detection of small, sub-clinical metastases (if present) and for visualization of the tumor’s invisible infiltration along the boundaries of the planned resection. The overall objective of this application is to clinically validate the use of a fluorescently labeled anti-EGFR antibody, panitumumab-IRDye800CW (pan800), for the intraoperative detection of low-volume (1-3 mm3) pancreatic cancer tumor foci in vivo. The central hypothesis is that Near InfraRed (NIR) intraoperative imaging with pan800 will enable ultrasensitive detection of tumor deposits that would otherwise escape detection using current imaging technology and surgical inspection/palpation. In the proposed study, patients with pancreatic adenocarcinoma eligible for surgery will undergo infusion of pan800 2-5 days prior to surgery and NIR cameras will be used intraoperatively to detect 1-3 mm³ tumor foci. The following two specific aims will be pursued: 1) Determine the diagnostic accuracy of pan800 intraoperative fluorescent imaging to detect radiographically occult (i.e., unseen by the radiologist) pancreatic adenocarcinoma metastases; and 2) Determine the efficacy of pan800 fluorescent imaging to identify visibly occult (i.e., unseen by the surgeon) residual tumor foci at the post-surgical resection bed in vivo or at the margin of the resected specimen ex vivo. Under the first aim, the sensitivity and specificity of this intraoperative imaging modality to identify small, sub-radiologic peritoneal metastases will be documented. For the second aim, the incremental yield of this modality over conventional bright-field inspection in identifying otherwise invisible tumor foci at the resection bed or specimen margin will be demonstrated. The repurposing of readily available therapeutic EGFR antibodies to surgical imaging agents is not only safe and cost effective, but also highly innovative, in the applicant’s opinion, as it can challenge the status quo related to intraoperative pancreatic cancer detection, which has not fundamentally changed over several decades. The proposed research is significant because it will build upon the previously demonstrated efficacy of pan800 to detect pancreatic cancer in vivo, providing new opportunities for its continued development as a tool to enhance intraoperative staging, support decision making, increase the likelihood of complete tumor resection, and eventually improve clinical outcomes for patients with this highly lethal malignancy.

Public health relevance public domain (NIH RePORTER)

PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on the clinical translation of a new antibody-based optical fluorescent technology for ultrasensitive detection of occult pancreatic cancer in vivo. The anticipated validation of this intraoperative molecular imaging method in identifying very small (1-3mm3) pancreatic cancer deposits will not only enhance surgical staging and outcomes for this highly lethal cancer, but can also lay the foundation for the development of new horizons for earlier detection of this challenging malignancy. As essentially every patient diagnosed with pancreatic cancer currently will eventually die of this disease, the proposed research is relevant to the part of the NIH’s mission that pertains to reducing illness and disability.