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分布的信息对于了解和预测化学品的作用和毒性非常重要。质谱成像（MSI）已成为一个重要的工具，在过去的十年中，它开始显示出潜力，在许多领域提供新的信息，由于其独特的能力，获得分子特异性图像，并提供多路复用的信息，而不需要标记或染色。在MSI中，研究表面上存在的分子的化学身份作为其空间分布的函数。除了目前涉及真空中MSI的标准方法，如基质辅助激光解吸电离（MALDI）和二次离子质谱（西姆斯），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），允许在质谱仪外的未处理样品在大气压下进行MSI。我们建议MSI的发展和应用的药物/农药在生物组织中的分布的生物模型。具体而言，我们将斑马鱼作为药物/农药或化学载体系统研究的生物模型，通过MSI实现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。该项目对制药公司非常感兴趣，这些公司试图更好地跟踪药物在特定组织中的代谢物，或识别和了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，有助于阐明生物化学/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中的药物和农药来帮助环境监测，并找到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.