Using advanced molecular imaging in drug discovery

To bring new medicines to patients faster and more effectively, we are constantly seeking ways to enhance our understanding of the diseases we want to treat. Using advanced molecular imaging – propelled most recently by mass spectrometry – our scientists are able to probe and analyse tissue samples in depth and detail that was previously impossible. By harnessing the powers of artificial intelligence (AI) and machine learning, the full molecular complexity is now becoming decipherable, and advanced imaging is already revealing insights that have the potential to transform future drug discovery and development.

What is molecular imaging?

Molecular imaging is an advanced form of imaging that enhances our understanding of the effects of drug compounds on human tissues at a cellular level. Our molecular imaging technologies allow us probe tissue samples – whether from patient biopsies, animal models or advanced cell cultures – in unprecedented depth.

Mass spectrometry imaging (MSI) stands out as a powerful type of molecular imaging, allowing us to better understand the human body’s molecular complexity and what exactly a candidate medicine is doing in a patient’s body. Using this technology, we are able to measure the individual masses of molecules – whether peptides, proteins, lipids, endogenous metabolites or drug molecules – using a mass spectrometer and simultaneously visualise their spatial distributions. Learnings from MSI offer vital clues to understand the inter-relationships of these molecules within the tissue microenvironment and allow us to better assess the safety and efficacy of our medicines.

Mass spectrometry is not new and has long been used in many areas of research and development; it relies on the process of ionisation - turning tissue samples into gaseous form. MSI stands apart because the tissue samples are not homogenised (mixed-up) before ionisation. Instead, the tissue is snap-frozen and ionised directly from its intact surface, so that each molecule’s original position is known. The whole sample is scanned a few microns at a time, providing a wealth of digital information. From this, we can generate vast datasets from healthy, diseased and drug-treated tissue samples and use AI and machine learning techniques to spot patterns, connections and relationships, turning information into insights and insights into knowledge.

Learn more about how science compels us to push the boundaries of what is possible in the below video:

We are also constantly striving to improve our techniques and methodologies for molecular imaging, including how we prepare and analyse our biological samples. We recently developed new sample processing protocols that are compatible across a diverse range of imaging technologies, allowing the same samples to be analysed across platforms. As a result, we can now integrate findings to create unprecedented views of the complex biology and unveil deeper insights within every sample of tissue.¹

Creating a ‘Google Earth’ view on a molecular scale

Today’s advanced molecular imaging techniques – and MSI in particular – enable our scientists to create detailed molecular maps. Much like Google Earth enables a satellite view of the planet down to 3D views of individual streets and buildings, our molecular imaging programme and capabilities allow us to zoom in and out of tissues from the micro to the macro level. Viewing samples in this way is revealing actionable insights that might otherwise be obscured within the biological complexity of the tissues.

Every molecule we detect has its own map, pieced together by tens of thousands of images from different perspectives. We can “see” drug molecules, disease biomarkers and the tissue microenvironment simultaneously and examine the picture from the genomic and molecular viewpoint up to the cellular, tissue, organ and patient level. For example, with this knowledge, we are paving the way for novel therapeutic development by deepening our knowledge of disease mechanisms,² combining the powers of molecular imaging with multi-omics to advance our understanding of cancer biology,^3,4 and assessing novel molecules that may aid cardioprotection – limiting the cellular damage caused by a heart attack.⁵