Expanding the Horizons of Imaging: Real-time Tracking of Drugs in the Brain

许多药物在临床试验中失败，尽管在临床前分析中显示出希望。在药物开发细目中的一个关键分析挑战是衡量有效剂量的给药药物是否在正确的时间和所需的持续时间到达正确的组织。因此，死亡率是最常用的衡量药物是否有效的指标。因此，显然需要开发新的分析工作流程，以提供对药物在组织中分布的详细了解。我们提出了一种新的工作流程，使用成像方法的组合来确定药物在体外、小鼠体内和切除组织中的实验分布。为了方法开发的目的，将调查一种已知的脑肿瘤靶向药物在小鼠组织和细胞中的分布。在这个工作流程中，磁共振成像(MRI)将用于对药物在小鼠大脑中的分布进行实时成像。这项技术将通过显微镜方法得到光学成像的支持，并使用来自同一动物的切除组织样本的质谱学成像进行验证，从而允许在磁共振成像、光学成像和质谱学成像之间进行直接比较。通过结合这些技术，将有可能全面、详细和实时地展示药物在大脑中的分布。这一工作流程将对从各种组织中分析替代药物具有很高的转化性。

Many drugs fail in clinical trials despite showing promise in preclinical analysis. A key analytical challenge in this drug development breakdown is in measuring whether an effective dose of the administered drug reaches the right tissue at the correct time and for the required duration. As a result, mortality (death) rate is the metric most commonly used to judge whether a drug works. Hence, there is a clear need for new analytical workflows to be developed that can offer a detailed understanding of drug distributions in tissues.We propose a new workflow using a combination of imaging approaches to determine drug distribution experimentally in vitro, in real-time in mice, and from excised tissue. For the purposes of method development, the distribution of a known brain tumour targeting drug will be investigated in mouse tissues and cells. In this workflow, magnetic resonance imaging (MRI) will be utilised for real-time imaging of drug distributions in the mouse brain. This technique will be supported by optical imaging via microscopy approaches and validated using mass spectrometry imaging of excised tissue samples from the same animal, allowing direct comparisons between the magnetic resonance, optical, and mass spectrometry imaging. By combining these techniques, it will be possible to comprehensively showcase drug distribution in the brain in detail and in real-time. This workflow will be highly translational for the analysis of alternative drugs from various tissues.