title: Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts.
abstract: 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.
authors.affiliation: Department of Physics, Purdue University, West Lafayette, Indiana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Merrill
authors.affiliation: Animated Dynamics, Inc., West Lafayette, Indiana.
authors.forename: Ran
authors.initials: R
authors.lastname: An
authors.affiliation: Department of Physics, Purdue University, West Lafayette, Indiana.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Bakhtiyor
authors.initials: B
authors.lastname: Yakubov
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.|Indiana University Simon Cancer Center, Roudebush VA Hospital, Indianapolis, Indiana.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana.|Animated Dynamics, Inc., West Lafayette, Indiana.
authors.forename: John
authors.initials: J
authors.lastname: Turek
authors.affiliation: Department of Physics, Purdue University, West Lafayette, Indiana.|Animated Dynamics, Inc., West Lafayette, Indiana.
authors.forename: David
authors.initials: D
authors.lastname: Nolte
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010984:Platinum / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D018608:Ultrasonography, Doppler / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D010984:Platinum