Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer
- 14 September 2014
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 74 (18), 5184-5194
- https://doi.org/10.1158/0008-5472.can-14-0663
Abstract
There is a need for technologies to predict the efficacy of cancer treatment in individual patients. Here, we show that optical metabolic imaging of organoids derived from primary tumors can predict the therapeutic response of xenografts and measure antitumor drug responses in human tumor–derived organoids. Optical metabolic imaging quantifies the fluorescence intensity and lifetime of NADH and FAD, coenzymes of metabolism. As early as 24 hours after treatment with clinically relevant anticancer drugs, the optical metabolic imaging index of responsive organoids decreased (P < 0.001) and was further reduced when effective therapies were combined (P < 5 × 10−6), with no change in drug-resistant organoids. Drug response in xenograft-derived organoids was validated with tumor growth measurements in vivo and staining for proliferation and apoptosis. Heterogeneous cellular responses to drug treatment were also resolved in organoids. Optical metabolic imaging shows potential as a high-throughput screen to test the efficacy of a panel of drugs to select optimal drug combinations. Cancer Res; 74(18); 5184–94. ©2014 AACR.Keywords
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