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Three-dimensional (3D) tissue cultures are replacing conventional two-dimensional (2D) cultures for applications in cancer drug development. However, direct comparisons of  in vitro  3D models relative to  in vivo  models derived from the same cell lines have not been reported because of the lack of sensitive optical probes that can extract high-content information from deep inside living tissue. Here we report the use of biodynamic imaging (BDI) to measure response to platinum in 3D living tissue. BDI combines low-coherence digital holography with intracellular Doppler spectroscopy to study tumor drug response. Human ovarian cancer cell lines were grown either  in vitro  as 3D multicellular monoculture spheroids or as xenografts in nude mice. Fragments of xenografts grown  in vivo  in nude mice from a platinum-sensitive human ovarian cell line showed rapid and dramatic signatures of induced cell death when exposed to platinum  ex vivo , while the corresponding 3D multicellular spheroids grown  in vitro  showed negligible response. The differences in drug response between  in vivo  and  in vitro  growth have important implications for predicting chemotherapeutic response using tumor biopsies from patients or patient-derived xenografts.

Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts