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Proceedings Paper

Metabolic autofluorescence imaging of head and neck cancer organoids quantifies cellular heterogeneity and treatment response (Conference Presentation)
Author(s): Amy T. Shah; Tiffany M. Heaster; Melissa C. Skala
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Paper Abstract

Treatment options for head and neck cancer are limited, and can cause an impaired ability to eat, talk, and breathe. Therefore, optimized and personalized therapies could reduce unnecessary toxicities from ineffective treatments. Organoids are generated from primary tumor tissue and provide a physiologically-relevant in vitro model to measure drug response. Additionally, multiphoton fluorescence lifetime imaging (FLIM) of the metabolic cofactors NAD(P)H and FAD can resolve dynamic cellular response to anti-cancer treatment. This study applies FLIM of NAD(P)H and FAD to head and neck cancer organoids. Head and neck cancer tissue was digested and grown in culture as three-dimensional organoids. Gold standard measures of therapeutic response in vivo indicate stable disease after treatment with cetuximab (antibody therapy) or cisplatin (chemotherapy), and treatment response after combination treatment. In parallel, organoids were treated with cetuximab, cisplatin, or combination therapy for 24 hours. Treated organoids exhibit decreased NAD(P)H lifetime (p<0.05) and increased FAD lifetime (p<0.05) compared with control organoids. Additionally, analysis of cellular heterogeneity identifies distinct subpopulations of cells in response to treatment. A quantitative heterogeneity index predicts in vivo treatment response and demonstrates increased cellular heterogeneity in organoids treated with cetuximab or cisplatin compared with combination treatment. Mapping of cell subpopulations enables characterization of spatial relationships between cell subpopulations. Ultimately, an organoid model combined with metabolic fluorescence imaging could provide a high-throughput platform for drug discovery. Organoids grown from patient tissue could enable individualized treatment planning. These achievements could optimize quality of life and treatment outcomes for head and neck cancer patients.

Paper Details

Date Published: 24 April 2017
PDF: 1 pages
Proc. SPIE 10068, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XV, 100680B (24 April 2017); doi: 10.1117/12.2252441
Show Author Affiliations
Amy T. Shah, Vanderbilt Univ. (United States)
Tiffany M. Heaster, Univ. of Wisconsin-Madison (United States)
Melissa C. Skala, Univ. of Wisconsin-Madison (United States)


Published in SPIE Proceedings Vol. 10068:
Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XV
Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, Editor(s)

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