Mass spectrometry imaging advances and application in pharmaceutical research

Mass spectrometry imaging advances and application in pharmaceutical research
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质谱成像的进展及其在药物研究中的应用

DOI:
10.15212/amm-2022-0046
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发表时间:
2022-12
期刊:
Acta Materia Medica
影响因子:
--
通讯作者:
Yifan Meng
Yifan Meng
中科院分区:
其他
文献类型:
--
作者:
Xiaowei Song;Chao Li;Yifan Meng

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质谱成像(MSI)已被证明是一个有价值的工具,几乎在临床前药物研究和开发(R&D)管道的每个阶段,甚至临床药物评价的早期阶段。MSI可以特异性地解析母体药物及其代谢产物在给药样本中的分布,而不会丢失空间信息,从而便于直接观察药物的药代动力学过程,例如吸收、分布、代谢和排泄。MSI可以同时显示数百种表型分子,包括蛋白质、聚糖、代谢物和脂质,它们在不同的生理区域具有独特的分布模式和生物功能。这种在化学和物理空间中的特征特异性使MSI成为探索药物药效学特性的理想分析技术,包括体外/体内功效、安全性、潜在毒性和可能的分子机制。MSI在药物研究中的应用也从传统的给药组织分析扩展到临床前药物研发管道的前端,例如研究结构-活性关系,高通量体外筛选以及对单细胞,类器官或肿瘤球体的离体研究。本文综述了MSI在药学研究中的应用,以及为满足这一中心需求而取得的技术和方法学进展。
Mass spectrometry imaging (MSI) has been shown to be a valuable tool through nearly every stage of the preclinical drug research and development (R&D) pipeline, and even to the early phase of clinical pharmaceutical evaluation. MSI can specifically resolve distributions of a parent drug and its metabolic products across dosed specimens without loss of spatial information, thus facilitating the direct observation of a drug’s pharmacokinetic processes, such as absorption, distribution, metabolism, and excretion. MSI can simultaneously visualize hundreds of phenotype molecules, including proteins, glycans, metabolites, and lipids, which have unique distribution patterns and biofunctions across different physiologic regions. This featured specificity in the chemical and physical spaces empowers MSI as an ideal analytical technique in exploring a drug’s pharmacodynamic properties, including in vitro/in vivo efficacy, safety, potential toxicity, and possible molecular mechanism. The application of MSI in pharmaceutical research has also been expanded from the conventional dosed tissue analysis to the front end of the preclinical drug R&D pipeline, such as investigating the structure-activity relationship, high-throughput in vitro screening, and ex vivo studies on single cells, organoids, or tumor spheroids. This review summarizes MSI application in pharmaceutical research accompanied by its technical and methodologic advances serving this central demand.
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