title: Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer.
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.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Walsh
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee. Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Cook
authors.affiliation: Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee. Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Sanders
authors.affiliation: Takis Biotech, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.affiliation: IRCCS National Cancer Institute "G. Pascale," Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee. Department of Medicine, Vanderbilt University, Nashville, Tennessee. Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee. m.skala@vanderbilt.edu.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Skala
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D061848:Optical Imaging; D009940:Organoids / Q000378:metabolism*; D011237:Predictive Value of Tests; D023041:Xenograft Model Antitumor Assays
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