Optical Coherence Tomography of Tumor Spheroids Identifies Candidates for Drug Repurposing in Ovarian Cancer
Optical Coherence Tomography of Tumor Spheroids Identifies Candidates for Drug Repurposing in Ovarian Cancer
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DOI：
10.1109/tbme.2022.3231835
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发表时间：
2022-12
影响因子：
4.6
通讯作者：
Feng Yan;J. Ha;Yuyang Yan;Sam Ton;Chen Wang;Bornface M. Mutembei;Zaid A. Alhajeri;Aubrey F. McNiel;Andrew J. Keddissi;Qinghao Zhang;M. Jayaraman;D. Dhanasekaran;Qinggong Tang
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文献类型：
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作者：
Feng Yan;J. Ha;Yuyang Yan;Sam Ton;Chen Wang;Bornface M. Mutembei;Zaid A. Alhajeri;Aubrey F. McNiel;Andrew J. Keddissi;Qinghao Zhang;M. Jayaraman;D. Dhanasekaran;Qinggong Tang
目的：多细胞肿瘤球体（MCT）是评估精确癌症治疗策略的药物疗效以及重新利用FDA批准的卵巢癌药物的不可或缺的模型。然而，目前的成像技术不能提供有效的监测病理反应，由于浅穿透和实验操作破坏。我们计划利用非侵入性光学成像工具来实现对MCT生长和治疗反应的体内纵向监测，以重新利用三种FDA批准的药物用于卵巢癌治疗。方法：使用扫频光源光学相干断层扫描（SS-OCT）系统监测MCT在11天内的体积生长。在第5天，使用浓度为1、10和25 µM的3种2-甲氧基炔雌醇（2-ME）、AZD 1208和R-酮咯酸（R-酮）抑制剂治疗卵巢MCT。应用三维（3D）、固有光衰减对比度和均匀度分析这些抑制剂对卵巢MCT的治疗效果。结果：我们发现浓度为10和25 µM的2-ME、AZD 1208和R-keto显著抑制卵巢MCT的体积增长。OCT结果显示，所有浓度的2-ME、AZD 1208和R-酮抑制剂对坏死组织均无影响。2-ME和AZD 1208抑制MCT内高度均匀组织的生长，且浓度越高，抑制效果越显著。结论：我们的研究结果表明，OCT能够可靠地监测卵巢MCT抑制剂的治疗效果，它可以用于未来卵巢癌新疗法的快速表征。
Objective: Multicellular tumor spheroids (MCTs) are indispensable models for evaluating drug efficacy for precision cancer therapeutic strategies as well as for repurposing FDA-approved drugs for ovarian cancer. However, current imaging techniques cannot provide effective monitoring of pathological responses due to shallow penetration and experimentally operative destruction. We plan to utilize a noninvasive optical imaging tool to achieve in vivo longitudinal monitoring of the growth of MCTs and therapeutic responses to repurpose three FDA-approved drugs for ovarian cancer therapy. Methods: A swept-source optical coherence tomography (SS-OCT) system was used to monitor the volume growth of MCTs over 11 days. Three inhibitors of 2-Methoxyestradiol (2-ME), AZD1208, and R-Ketorolac (R-keto) with concentrations of 1, 10, and 25 µM were employed to treat ovarian MCTs on day 5. Three-dimensional (3D), intrinsic optical attenuation contrast, and degree of uniformity were applied to analyze the therapeutic effect of these inhibitors on ovarian MCTs. Results: We found that 2-ME, AZD1208, and R-keto with concentration of 10 and 25 µM significantly inhibited the volume growth of ovarian MCTs. There was no effect to necrotic tissues from all concentrations of 2-ME, AZD1208, and R-keto inhibitors from our OCT results. 2-ME and AZD1208 inhibited the growth of high uniformity tissues within MCTs and higher concentrations provided more significant inhibitory effects. Conclusion: Our results indicated that OCT was capable and reliable to monitor the therapeutic effect of inhibitors to ovarian MCTs and it can be used for the rapid characterization of novel therapeutics for ovarian cancers in the future.