Biomolecular Mass Spectrometry Imaging, National Resource for Mass Spectrometry Imaging, Science for Life Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124, Uppsala, Sweden.
Pathology Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
Neuroimage. 2018 May 15;172:808-816. doi: 10.1016/j.neuroimage.2018.01.013. Epub 2018 Jan 10.
There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies.
目前非常需要开发能够同时提供几种分子物种详细脑定位信息的定量成像方法。此外，还需要广泛了解血脑屏障对神经活性化合物穿透、分布和疗效的影响。因此，我们开发了一种质谱成像方法，以可视化和定量检测具有不同血脑屏障通透性的药物在脑内的分布。通过这种方法，我们能够确定不同药物的血脑屏障转运，并由于提供了高空间分辨率，能够定义非常小的脑结构（例如脉络丛）中的药物分布。同时，我们通过抑制膜转运蛋白多药耐药蛋白 1 来研究药物-药物相互作用的影响。我们提出，所描述的方法可以作为神经活性药物开发过程中的有价值的分析工具，因为它可以提供传统成像技术经常忽略的生理相关信息。
