Non-Destructive Evaluation of Regional Cell Density Within Tumor Aggregates Following Drug Treatment

Roberge, Cassandra L.; Barroso, Margarida; Corr, David T.

doi:10.3791/64030

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…Volumetric growth of tumor spheroids was quantified using standard OCT imaging 24 . In addition, the regional differences in tumor spheroid drug response have been evaluated using OCT-based cell density quantification 25 .…”

Section: Introductionmentioning

confidence: 99%

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography

Abd El-Sadek,

Shen,

Mori

et al. 2023

Sci Rep

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This study aims at demonstrating label-free drug-response-patterns assessment of different tumor spheroids and drug types by dynamic optical coherence tomography (D-OCT). The study involved human breast cancer (MCF-7) and colon cancer (HT-29) spheroids. The MCF-7 and HT-29 spheroids were treated with paclitaxel (Taxol; PTX) and the active metabolite of irinotecan SN-38, respectively. The drugs were applied with 0 (control), 0.1, 1, and 10 μM concentrations and the treatment durations were 1, 3, and 6 days. A swept-source OCT microscope equipped with a repeated raster scanning protocol was used to scan the spheroids. Logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS$$_l$$ l ) algorithms were used to visualize the tumor spheroid dynamics. LIV and OCDS$$_l$$ l images visualized different response patterns of the two types of spheroids. In addition, spheroid morphology, LIV, and OCDS$$_l$$ l quantification showed different time-courses among the spheroid and drug types. These results may indicate different action mechanisms of the drugs. The results showed the feasibility of D-OCT for the evaluation of drug response patterns of different cell spheroids and drug types and suggest that D-OCT can perform anti-cancer drug testing.

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Section: Introductionmentioning

confidence: 99%

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography

Abd El-Sadek,

Shen,

Mori

et al. 2023

Sci Rep

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“…While the assays performed herein did not allow for inferences into the location of dead/dying cells, future work should seek to expand these results by incorporating information about cell viability with respect to location. A recently published technique from our lab uses the same OCT imaging modality with more in-depth Imaris image analysis to track regional cell death in drugged aggregate models, which is expected to help provide a clearer picture as to where a drug is acting most strongly.…”

Section: Resultsmentioning

confidence: 99%

Sophorolipid Candidates Demonstrate Cytotoxic Efficacy against 2D and 3D Breast Cancer Models

et al. 2023

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Sophorolipids are biosurfactants derived from the nonpathogenic yeasts such as Starmerella bombicola with potential efficacy in anticancer applications. Simple and cost-effective synthesis of these drugs makes them a promising alternative to traditional chemotherapeutics, pending their success in preliminary drug-screening. Drug-screening typically utilizes 2D cell monolayers due to their simplicity and ease of high-throughput assessment. However, 2D assays fail to capture the complexity and 3D context of the tumor microenvironment and have consequently been implicated in the high percentage of drugs investigated in vitro that later fail in clinical trials. Herein, we screened two sophorolipid candidates and a clinically-used chemotherapeutic, doxorubicin, on in vitro breast cancer models ranging from 2D monolayers to 3D spheroids, employing optical coherence tomography to confirm these morphologies. We calculated corresponding IC50 values for these drugs and found one of the sophorolipids to have comparable toxicities to the chemotherapeutic control. Our findings show increased drug resistance associated with model dimensionality, such that all drugs tested showed that 3D spheroids exhibited higher IC50 values than their 2D counterparts. These findings demonstrate promising preliminary data to support the use of sophorolipids as a more affordable alternative to traditional clinical interventions and demonstrate the importance of 3D tumor models in assessing drug response.

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“…In addition, the quantification of the volume and growth of a tumor spheroid was recently demonstrated using standard OCT imaging 26 . Furthermore, OCT-based tissue density quantification was used for evaluating regional differences in the drug response of tumor spheroids 27 . However, these methods quantify only the static properties of the tissue.…”

Section: Introductionmentioning

confidence: 99%

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

El-Sadek,

Morishita,

Mori

et al. 2023

Preprint

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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 (OCDSl) 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 OCDSlover treatment time. The spheroids treated with PTX had decreasing volumes and decrease of LIV and OCDSlsignals 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 OCDSlsignals decreased over treatment time at all DOX concentrations. The D-OCT, particularly OCDSl, 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.

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Non-Destructive Evaluation of Regional Cell Density Within Tumor Aggregates Following Drug Treatment

Cited by 6 publications

References 29 publications

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography

Sophorolipid Candidates Demonstrate Cytotoxic Efficacy against 2D and 3D Breast Cancer Models

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

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