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首页> 外文期刊>Scientific reports. >3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors
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3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

机译：3D质谱成像揭示在肿瘤中一个非常庞杂的药品流通

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Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse.
机译：质谱成像（MSI）是一种广泛的技术，用于定性描述在两维中的内源性或外源化合物在组织切片内的分布。使用MSI的药物绝对量化是最近在过去几年开始解决的挑战。从二维MSI协议开始，我们开发了一种三维管道，以研究肿瘤的药物渗透，并通过MALDI MSI开发一种新的药物量化方法。在恶性胸腔间皮瘤（MPM）的3D模型中测量不同肿瘤中的紫杉醇分布和浓度，这已知是一种非常异质的肿瘤，对不同的药物具有高度耐药性。 3D计算重建允许准确描述肿瘤PTX渗透，由于复杂的微环境而添加有关肿瘤药物分布的异质性的信息。使用内标在组织切片上均匀喷涂，确保与使用HPLC获得的定量结果。 3D模型提供了有关不同肿瘤子体积中药物浓度的重要信息，并表明该药物未达到每种肿瘤的大部分，表明伪阻力的概念，作为无效疗法和肿瘤复发的进一步解释。

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