Quantitative Imaging of Morphometric and Metabolic Signatures Reveals Heterogeneity in Drug Response of Three-Dimensional Mammary Tumor Spheroids

Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
V Krishnan Ramanujan

Abstract

In order to monitor the drug responses of three-dimensional mammary tumor spheroids and to elucidate the role of inter- and intra-spheroid heterogeneity in determining drug sensitivity in the spheroids, an integrated image analysis framework was developed for morphometric and metabolic characterization of the three-dimensional tumor spheroids. Three-dimensional spheroid cultures of primary mammary tumor epithelial cells isolated from freshly excised tumors from a transgenic mouse model of adenocarcinoma (MMTV-PyMT) were imaged by using vital dyes and mitochondrial membrane potential markers. Custom-developed java and python program codes facilitated image processing, numerical computation, and graphical analysis of large datasets generated from the experiments. A panel of cancer drugs (rapamycin, BEZ235, MK2206, and flavopiridol) was tested to determine the degree of drug sensitivity as well as heterogeneity in drug response. A new quantitative metric (growth/toxicity) was developed based on morphometric parameters that were found to track the growth and apoptotic cell populations. Further, this study identified two parameters, namely, skew and kurtosis-which report the spatial heterogeneity in mitochondrial metabolism within t...Continue Reading

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Citations

Mar 19, 2020·World Journal of Stem Cells·Gabriela S KronembergerLeandra Santos Baptista
Apr 26, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lin Z LiArjun G Yodh
Apr 17, 2021·Nature Methods·Lorenzo ScipioniEnrico Gratton

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