Development and Application of Mass Spectrometry Imaging to Biological Models.

关于药物和农药及其代谢物在组织中的分布的信息对于理解和预测化学物质的作用和毒性非常重要。质谱成像（MSI）在过去十年中已经成为一种重要的工具，并且由于其独特的获取分子特异性图像的能力以及无需标记或染色即可提供多路信息的能力，它开始显示出在许多领域提供新信息的潜力。在MSI中，存在于表面上的分子的化学特性作为其空间分布的函数进行了研究。除了现在的标准方法涉及真空中的MSI，如基质辅助激光解吸电离（MALDI）和二次离子质谱（SIMS），最近开发的环境电离技术，如解吸电喷雾电离（DESI）和解吸大气压光电离（DAPPI），允许MSI在大气压下未经处理的样品在质谱仪外。我们建议将MSI应用于药物/农药在生物组织中的分布的生物学模型。具体来说，我们将把斑马鱼描述为药物/农药或化学载体系统研究的生物学模型，以实现MSI的靶向治疗和毒理学分析。我们还将研究不同的材料，用于直接或间接分析不同菌株相互作用时释放的化学介质。这个项目对制药公司来说非常有兴趣，他们试图更好地跟踪特定组织中药物的代谢物，或者识别和理解细菌相互作用中的化学介质。这项工作将有利于学术界和制药公司，有助于阐明生化/毒理学途径，并有助于未来的结构- adme研究，以开发具有更好活性和更低毒性的新分子。此外，在未来，该项目可以通过分析野生动物体内的药物和农药来帮助环境监测，并发现新的潜在抗生素来治疗细菌感染。

Information about the distribution of drugs and pesticides and their metabolites in tissues is important for understanding and predicting a chemical's action and toxicity. Mass Spectrometry Imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of their spatial distribution. In addition to now standard methods involving MSI in vacuum such as matrix-assisted laser desorption ionization (MALDI) and secondary-ion mass spectrometry (SIMS), recently developed ambient ionization techniques, such as desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI), allow MSI under atmospheric pressure of untreated samples outside the mass spectrometer. We propose the development and application of MSI to biological models of drug/pesticide distribution in biological tissues. Specifically, we will characterize the zebrafish as a biological model for studies of drugs/pesticides or chemical vector systems to achieve targeted therapy and toxicological analysis by MSI. We also will investigate different materials for direct or indirect analysis of chemical mediators released when different strains of bacteria interact. This project is of great interest to pharmaceutical companies trying to better track metabolites of drugs in specific tissues or to identify and understand chemical mediators in bacterial interactions. The work would benefit both academics and pharmaceutical companies, helping in the elucidation of the biochemical/toxicological pathways and, assist future structure-ADME studies for the development of new molecules with better activity and less toxicity. Moreover, in the future this project could help environmental monitoring by analyzing drugs and pesticides in wild animals and find new potential antibiotics to treat bacterial infections.