Unit of Computational Biology, Research and Innovation Centre , Fondazione Edmund Mach , via E. Mach 1 , 38010 San Michele all'Adige , Italy.
Nanotechnology in Medicinal Chemistry, Department of Molecular Biotechnology and Health Sciences , Università di Torino , 10124 Torino , Italy.
Anal Chem. 2018 Nov 20;90(22):13257-13264. doi: 10.1021/acs.analchem.8b01870. Epub 2018 Nov 8.
Enhancing drug penetration in solid tumors is an interesting clinical issue of considerable importance. In preclinical research, mass-spectrometry imaging is a promising technique for visualizing drug distribution in tumors under different treatment conditions and its application in this field is rapidly increasing. However, in view of the huge variability among MSI data sets, drug homogeneity is usually manually assessed by an expert, and this approach is biased by interobserver variability and lacks reproducibility. We propose a new texture-based feature, the drug-homogeneity index (DHI), which provides an objective, automated measure of drug homogeneity in MSI data. A simulation study on synthetic data sets showed that previously known texture features do not give an accurate picture of intratumor drug-distribution patterns and are easily influenced by the tumor-tissue morphology. The DHI has been used to study the distribution profile of the anticancer drug paclitaxel in various xenograft models, which were either pretreated or not pretreated with antiangiogenesis compounds. The conclusion is that drug homogeneity is better in the pretreated condition, which is in agreement with previous experimental findings published by our group. This study shows that DHI could be useful in preclinical studies as a new parameter for the evaluation of protocols for better drug penetration.
提高实体瘤中的药物渗透是一个非常重要的临床问题。在临床前研究中，质谱成像技术是一种很有前途的技术，可以在不同的治疗条件下可视化肿瘤中的药物分布，并且它在该领域的应用正在迅速增加。然而，鉴于 MSI 数据集之间存在巨大的可变性，药物均匀性通常由专家手动评估，这种方法受到观察者间变异性的影响，缺乏可重复性。我们提出了一种新的基于纹理的特征，即药物均匀性指数（DHI），它为 MSI 数据中的药物均匀性提供了一种客观、自动化的测量方法。在对合成数据集的模拟研究表明，先前已知的纹理特征并不能准确反映肿瘤内药物分布模式，并且容易受到肿瘤组织形态的影响。DHI 已被用于研究抗癌药物紫杉醇在各种异种移植模型中的分布情况，这些模型要么经过抗血管生成化合物预处理，要么没有经过预处理。结论是预处理条件下的药物均匀性更好，这与我们小组之前发表的实验结果一致。这项研究表明，DHI 可以作为评估更好的药物渗透方案的新参数，在临床前研究中很有用。
