title: Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT.
abstract: Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.
authors.affiliation: Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, CNY149-3, 13th St, Charlestown, MA USA.
authors.forename: Yookyung
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, CNY149-3, 13th St, Charlestown, MA USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Klein
authors.affiliation: Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, CNY149-3, 13th St, Charlestown, MA USA.
authors.forename: Hequn
authors.initials: H
authors.lastname: Wang
authors.affiliation: Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, CNY149-3, 13th St, Charlestown, MA USA.
authors.forename: Conor L
authors.initials: CL
authors.lastname: Evans
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013843:Thiazines / Q000494:pharmacology; D041623:Tomography, Optical Coherence / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D017319:Photosensitizing Agents; D013843:Thiazines; C081287:5-ethylamino-9-diethylaminobenzo(a)phenothiazinium; D016190:Carboplatin