Label-free visualization and quantification of the drug-type-dependent response of tumor spheroids by dynamic optical coherence tomography

ABSTRACT We demonstrate label-free dynamic optical coherence tomography (D-OCT)-based visualization and quantitative assessment of patterns of tumor spheroid response to three anti-cancer drugs. The study involved treating human breast adenocarcinoma (MCF-7 cell-line) with paclitaxel (PTX), tamoxifen citrate (TAM), and doxorubicin (DOX) at concentrations of 0 (control), 0.1, 1, and 10 μM for 1, 3, and 6 days. In addition, fluorescence microscopy imaging was performed for reference. The D-OCT imaging was performed using a custom-built OCT device. Two algorithms, namely logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS l ) were used to visualize the tissue dynamics. The spheroids treated with 0.1 and 1 μM TAM appeared similar to the control spheroid, whereas those treated with 10 μM TAM had significant structural corruption and decreasing LIV and OCDS l over treatment time. The spheroids treated with PTX had decreasing volumes and decrease of LIV and OCDS l signals over time at most PTX concentrations. The spheroids treated with DOX had decreasing and increasing volumes over time at DOX concentrations of 1 and 10 μM, respectively. Meanwhile, the LIV and OCDS l signals decreased over treatment time at all DOX concentrations. The D-OCT, particularly OCDS l , patterns were consistent with the fluorescence microscopic patterns. The diversity in the structural and D-OCT results among the drug types and among the concentrations are explained by the mechanisms of the drugs. The presented results suggest that D-OCT is useful for evaluating the difference in the tumor spheroid response to different drugs and it can be a useful tool for anti-cancer drug testing.