There is a critical need to predict effective treatments for individual cancer patients. The goal of this work is to validate Optical Metabolic Imaging (OMI) of tumor-derived organoids as a predictive drug screening platform in breast and pancreatic cancer, by relating multiphoton fluorescence lifetime imaging (FLIM) data from these organoids to clinical patient outcomes. Three-dimensional organoids were generated from core needle biopsies of breast tumors and surgically resected pancreatic ductal adenocarcinomas (PDAC). These organoids were treated with the patient’s prescribed therapy, and early metabolic changes were measured using multiphoton FLIM of the metabolic co-enzymes NAD(P)H and FAD at the single-cell level. Changes were quantified using the OMI Index, a linear combination of the optical redox ratio (ratio of the fluorescence intensities of NAD(P)H to FAD), and the mean NAD(P)H and FAD fluorescence lifetimes. Organoids grew from a variety of untreated breast tumor subtypes including triple negative, HER2+, and ER+/PR+/HER2-, and early metabolic changes could be resolved at the single-cell level after only 24 hours of treatment in vitro. Surgical pathology 2-7 months after completing neoadjuvant treatment served as gold standard validation of breast cancer patient drug response. Organoids were also successfully grown from surgically resected PDAC samples, and included two subtypes of epithelial cells as well as stromal fibroblasts. Patient follow-up data after surgery and subsequent treatment was used as gold standard validation of PDAC patient drug response. This platform shows promise for predicting long-term response to therapy in breast and pancreatic cancer patients.
Joe T. Sharick, Alexandra J. Walsh, Melinda E. Sanders, Mark C. Kelley, Ingrid M. Meszoely, Mary A. Hooks, Alexander A. Parikh, and Melissa C. Skala, "Predicting patient response to therapy in pancreatic and breast cancer using optical metabolic imaging (Conference Presentation)," Proc. SPIE 10068, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XV, 1006806 (Presented at SPIE BiOS: January 30, 2017; Published: 15 August 2017); https://doi.org/10.1117/12.2253431.5380018872001.
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