Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response

• Published in: Pancreas Vol. 45; no. 6; p. 863
• Main Authors: Walsh, Alex J, Castellanos, Jason A, Nagathihalli, Nagaraj S, Merchant, Nipun B, Skala, Melissa C
• Format: Journal Article
• Language: English
• Published: United States 01.07.2016
• Subjects: Animals; Antineoplastic Agents - pharmacology; Carcinoma, Pancreatic Ductal - diagnostic imaging; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Humans; Mice, Knockout; Microscopy, Fluorescence, Multiphoton - methods; Optical Imaging - methods; Organoids - diagnostic imaging; Organoids - drug effects; Organoids - metabolism; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Reproducibility of Results; Sensitivity and Specificity; Time Factors
• ISSN: 1536-4828
• DOI: 10.1097/mpa.0000000000000543

Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantitative end point, the OMI index, is evaluated as a biomarker of drug response in pancreatic cancer organoids. Optical metabolic imaging is used to assess both malignant cell and fibroblast drug response within primary murine and human pancreatic cancer organoids. Anticancer drugs induce significant reductions in the OMI index of murine and human pancreatic cancer organoids. Subpopulation analysis of OMI data revealed heterogeneous drug response and elucidated responding and nonresponding cell populations for a 7-day time course. Optical metabolic imaging index significantly correlates with immunofluorescence detection of cell proliferation and cell death. Optical metabolic imaging of primary pancreatic ductal adenocarcinoma organoids is highly sensitive to drug-induced metabolic changes, provides a nondestructive method for monitoring dynamic drug response, and presents a novel platform for patient-specific drug testing and drug development.