Pancreas Cancer Specific Probe for Image Guided Resection

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Pancreas Cancer Specific Probe for Image Guided Resection This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-100. The incidence of pancreatic ductal adenocarcinoma (PDAC) continues to rise as does the number of patients eligible for surgical resection due to improvements in neoadjuvant therapy. Surgical resection with negative resection margins remains the only opportunity for cure for patients with this disease. However, microscopically positive resection margins have been reported in up to 75% of patients undergoing resection for curative intent. Clinically available imaging techniques lack the ability to detect microscopic tumor involvement of mesenteric vessels or differentiate between fibrosis and live tumor, representing an unmet clinical need. Development of a PDAC specific near infrared (NIR) contrast agent that can be detected by multispectral optoacoustic tomography (MSOT) would improve intraoperative detection of resection margin. This proposal will synthesize a NIR reporter agent that targets plectin-1 peptide, which is aberrantly located on the surface of PDAC cells. Our synthesized probe will be optimized for binding with human PDAC. Specificity of the probe will be tested on human PDAC cell lines and tissue collected from resected PDAC. The most efficiently performing probe will then be tested for toxicity and performance in vivo in mice. Successful completion of this proposal will generate a PDAC-specific contrast probe to improve detection of viable PDAC and adjacent fibrosis in vivo using MSOT and NIR fluorescence.