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

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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.