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

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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.