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Optical metabolic imaging of heterogeneous drug response in pancreatic cancer patient organoids

New tools are needed to match pancreatic cancer patients with effective treatments. Patient-derived organoids offer a high-throughput platform to personalize treatments and discover novel therapies. Currently, methods to evaluate drug response in organoids are limited because they cannot be completed in a clinically relevant time frame, only evaluate response at one time point, and most importantly, overlook cellular heterogeneity. In this study, non-invasive optical metabolic imaging (OMI) of cellular heterogeneity in organoids was evaluated as a predictor of clinical treatment response. Organoids were generated from fresh patient tissue samples acquired during surgery and treated with the same drugs as the patient’s prescribed adjuvant treatment. OMI measurements of heterogeneity in response to this treatment were compared to later patient response, specifically to the time to recurrence following surgery. OMI was sensitive to patient-specific treatment response in as little as 24 hours. OMI distinguished subpopulations of cells with divergent and dynamic responses to treatment in living organoids without the use of labels or dyes. OMI of organoids agreed with long-term therapeutic response in patients. With these capabilities, OMI could serve as a sensitive high-throughput tool to identify optimal therapies for individual pancreatic cancer patients, and to develop new effective therapies that address cellular heterogeneity in pancreatic cancer. Significance OMI can non-invasively quantify cellular-level heterogeneity in treatment response within pancreatic cancer patient-derived organoids, which could enable high-throughput drug screens to personalize treatment for individual patients and to accelerate drug discovery.