Diffuse reflectance spectroscopy to monitor murine colorectal tumor progression and therapeutic response

Diffuse reflectance spectroscopy to monitor murine colorectal tumor progression and therapeutic response
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DOI:
10.1117/1.jbo.25.3.035002
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发表时间:
2020-03-01
影响因子:
3.5
通讯作者:
Muldoon,Timothy J.
Muldoon,Timothy J.
中科院分区:
医学3区
文献类型:
--
作者:
Mundo,Ariel;Greening,Gage J.;Muldoon,Timothy J.

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意义:许多结直肠癌(CRC)研究使用小鼠异位肿瘤模型来确定对治疗的反应。然而,这些模型不能复制CRC的肿瘤微环境。通过漫反射光谱(DRS)从小鼠原发性CRC肿瘤中获得的治疗反应的生理信息为开发新药物和CRC给药策略提供了更好的理解。目的:通过DRS定量原发性CRC模型中肿瘤对化疗的反应,以提取组织中的总血红蛋白含量(tHb)、氧饱和度(StO 2)、氧合血红蛋白和脱氧血红蛋白。多模式DRS和成像探头(外径0.78 mm)的设计和验证,以获得扩散光谱,通过内窥镜引导,在发展中的结肠肿瘤在5-氟尿嘧啶(5-FU)最大耐受(MTD)和节拍方案。结果:MTD和节拍化疗组小鼠原发性CRC肿瘤在新辅助化疗第4周时StO 2均出现最大增加,为21 ± 6%,与对照组相比,差异有显著性(P < 0. 05)。   17 ± 6%   变化,分别。tHb.Conclusion:我们的研究表明,DRS的可行性,以量化对治疗的反应,在原发性结直肠癌模型。
Significance:Many studies in colorectal cancer (CRC) use murine ectopic tumor models to determine response to treatment. However, these models do not replicate the tumor microenvironment of CRC. Physiological information of treatment response derived via diffuse reflectance spectroscopy (DRS) from murine primary CRC tumors provide a better understanding for the development of new drugs and dosing strategies in CRC.Aim:Tumor response to chemotherapy in a primary CRC model was quantified via DRS to extract total hemoglobin content (tHb), oxygen saturation (StO2), oxyhemoglobin, and deoxyhemoglobin in tissue.Approach:A multimodal DRS and imaging probe (0.78 mm outside diameter) was designed and validated to acquire diffuse spectra longitudinally—via endoscopic guidance—in developing colon tumors under 5-fluoruracil (5-FU) maximum-tolerated (MTD) and metronomic regimens. A filtering algorithm was developed to compensate for positional uncertainty in DRS measurementsResults:A maximum increase in StO2was observed in both MTD and metronomic chemotherapy-treated murine primary CRC tumors at week 4 of neoadjuvant chemotherapy, with 21  ±  6  %   and 17  ±  6  %   fold changes, respectively. No significant changes were observed in tHb.Conclusion:Our study demonstrates the feasibility of DRS to quantify response to treatment in primary CRC models.