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Updated: Mar 8, 2026
Author Spotlight: Developing Multiplexed Kinetic Assays for Organoid-Based Drug Response Analysis
Published on: January 5, 2024
Metabolic Imaging of Head and Neck Cancer Organoids
Amy T Shah1, Tiffany M Heaster1,2, Melissa C Skala1,2,3
1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States of America.
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.
Insights
Optical metabolic imaging of head and neck cancer organoids rapidly detects treatment response. This high-throughput assay can streamline drug discovery for improved head and neck cancer therapies.
Area of Science:
- Biomedical Engineering
- Oncology
- Optical Imaging
Background:
- Head and neck cancers present significant treatment challenges, leading to patient morbidity and mortality.
- Current drug discovery for these cancers is lengthy and costly, necessitating optimized assay development.
- Improved therapeutic strategies are crucial to minimize patient toxicities and improve outcomes.
Purpose of the Study:
- To apply optical metabolic imaging to three-dimensional head and neck cancer organoids for evaluating therapeutic response.
- To assess the sensitivity and resolution of optical metabolic imaging in detecting treatment effects at a single-cell level.
- To explore the potential of this platform as a high-throughput assay for streamlining head and neck cancer drug discovery.
Main Methods:
- Utilized three-dimensional in vitro cultures (organoids) derived from primary head and neck tumor tissue.
- Employed optical imaging to measure intrinsic fluorescence from NAD(P)H and FAD, reflecting cell metabolism.
- Analyzed organoids before and after treatment with standard therapies (antibody, chemotherapy, combination) and assessed cellular heterogeneity.
Main Results:
- Optical metabolic imaging demonstrated sensitivity to therapeutic response in organoids within one day of treatment (p<0.05).
- The technique successfully resolved cell subpopulations exhibiting distinct metabolic phenotypes.
- Validation against gold standard measures (proliferation, cell death, in vivo tumor volume) confirmed therapeutic efficacy.
Conclusions:
- Optical metabolic imaging is a sensitive tool for assessing therapeutic response in head and neck cancer organoids.
- This platform can resolve cellular heterogeneity and identify distinct metabolic subpopulations.
- The developed assay has the potential to accelerate drug discovery and development for head and neck cancer treatments.
