Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest human malignancies with an extremely poor 5-year survival rate of below 5%. Surgical resection is the most effective treatment of choice because chemotherapy and radiation therapy do not significantly improve life expectancy. Residual tumor after PDAC surgery is common due to lack of PDAC targeted intraoperative contrast agents to confirm clear margins. Fluorescence imaging has the potential to improve surgery outcome and PDAC patients’ survival rate via the use of highly PDAC-specific molecular probes to facilitate tumor identification. We designed a focused library of 1-substituted benzo[c]xanthene fluorophores to image PDAC using ‘drug-like’ properties as quantitative descriptors for predicting and optimizing biodistribution and tissue targeting. Selective imaging of PDAC margins both in vivo, in a PDAC mouse model, and ex vivo, in human cryosections, with high signal-to-noise ratio, was attained. Optimization of the ex vivo staining conditions including fluorophore concentration, incubation and washing times have resulted in a simple and rapid imaging protocol that is amenable to clinical workflow. Automation using receiver operator characteristic (ROC) curve analysis enables quantification of the contrast between cancerous and healthy tissue.

Benzoxanthene probes with inherent pancreatic ductal adenocarcinoma selectivity

2019 Fall National Meeting

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