Development of bioorthogonal stimulated Raman scattering microscopy for evaluation of drug biodistribution

本项目将探索新型多模态成像和生物正交标记技术的开发和应用，以增强药物和相关药效学生物标志物的临床前评估。这是一个多学科的方法，包括新的化学和国家的最先进的成像技术。它建立在我们的专业知识基础上，使用多模态成像平台，通过将光谱上不同的拉曼物种与荧光报告结合起来，允许受激拉曼散射（SRS）将药物摄取映射到表型反应。SRS在亚细胞水平上提供药物分布的时间和空间测量的独特能力提供了改变我们对细胞内药物分布和作用机制的理解以及对药物发现计划的影响的潜力。该项目将提供证据，证明SRS成像是定量评估细胞内药物浓度的有力工具。展示SRS成像药物的能力，从而提供作用机制和药物在组织内的保留和分布的额外读数，将进一步支持鼓励工业界采用该技术。

This project will explore the development and application of novel multi-modal imaging and bioorthogonal tagging technologies to enhance the preclinical evaluation of drugs and associated pharmacodynamic biomarkers. This is a multidisciplinary approach encompassing novel chemistry and state-of-the art imaging technologies. It builds on our expertise using a multi-modal imaging platform that allows stimulated Raman scattering (SRS) mapping of drug uptake to phenotypic responses by combining spectroscopically distinct Raman species with fluorescent reporters. The unique capabilities of SRS in providing temporal and spatial measurements of drug distribution at the subcellular level offers the potential to transform our understanding of intracellular drug distribution and mechanism of action and impact on drug discovery programs. This project will provide evidence that SRS imaging is a powerful tool for the quantitative assessment of intracellular drug concentrations. Demonstration of the capacity of SRS to image drugs, thus giving additional readouts of mechanism of action and drug retention and distribution within tissues, will provide further support to encourage uptake of the technology by industry.