title: Metabolic Imaging of Head and Neck Cancer Organoids.
abstract: Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model. Head and neck cancer organoids are characterized alone and after treatment with standard therapies, including an antibody therapy, a chemotherapy, and combination therapy. Additionally, organoid cellular heterogeneity is analyzed quantitatively and qualitatively. Gold standard measures of treatment response, including cell proliferation, cell death, and in vivo tumor volume, validate therapeutic efficacy for each treatment group in a parallel study. Results indicate that optical metabolic imaging is sensitive to therapeutic response in organoids after 1 day of treatment (p<0.05) and resolves cell subpopulations with distinct metabolic phenotypes. Ultimately, this platform could provide a sensitive high-throughput assay to streamline the drug discovery process for head and neck cancer.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Amy T
authors.initials: AT
authors.lastname: Shah
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States of America.|Department of Biomedical Engineering, University of Wisconsin, Madison, WI, United States of America.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Heaster
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States of America.|Department of Biomedical Engineering, University of Wisconsin, Madison, WI, United States of America.|Morgridge Institute for Research, Madison, WI, United States of America.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Skala
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D000068818:Cetuximab / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D005456:Fluorescent Dyes; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D009940:Organoids / Q000000981:diagnostic imaging* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab; D005456:Fluorescent Dyes; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse