Development and Application of Mass Spectrometry Imaging to Biological Models.

关于药物和杀虫剂及其代谢物在组织中的分布的信息对于了解和预测一种化学物质的作用和毒性很重要。质谱学成像(MSI)是近十年来兴起的一种重要工具，由于其独特的获取分子特定图像和提供多路信息而不需要标记或染色的能力，它开始显示出在许多领域提供新信息的潜力。在MSI中，研究了存在于表面的分子的化学同一性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)和二次离子质谱仪(SIMS)，最近发展的环境电离技术，如解吸电喷雾电离(DESI)和解吸大气压光电离(DAPPI)，允许在大气压下对质谱仪外的未经处理的样品进行MSI。我们建议将MSI发展并应用于药物/农药在生物组织中分布的生物学模型。具体地说，我们将斑马鱼定性为研究药物/杀虫剂或化学媒介系统的生物模型，以实现MSI的靶向治疗和毒理学分析。我们还将调查不同的材料，直接或间接分析不同菌株相互作用时释放的化学介体。该项目对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的制药公司非常感兴趣。这项工作将使学者和制药公司受益，有助于阐明生化/毒理学途径，并有助于未来结构-ADME研究，以开发活性更好、毒性更低的新分子。此外，在未来，该项目可以通过分析野生动物中的药物和杀虫剂来帮助环境监测，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.