The emergence of imaging mass spectrometry in drug discovery and development: Making a difference by driving decision making.

The pharmaceutical industry is a dynamic, science-driven business constantly under pressure to innovate and morph into a higher performing organization. Innovations can include the implementation of new technologies, adopting new scientific methods, changing the decision-making process, compressing timelines, or making changes to the organizational structure. The drivers for the constant focus on performance improvement are the high cost of R&D as well as the lengthy timelines required to deliver new medicines for unmet needs. Successful innovations are measured against both the quality and quantity of potential new medicines in the pipeline and the delivery to patients. In this special feature article, we share our collective experience implementing matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technology as an innovative approach to better understand the tissue biodistribution of drugs in the early phases of drug discovery to establish pharmacokinetic-pharmacodynamic (PK-PD) relationships, as well as in the development phase to understand pharmacology, toxicology, and disease pathogenesis. In our experience, successful implementation of MALDI IMS in support of therapeutic programs can be measured by the impact IMS studies have on driving decision making in pipeline progression. This provides a direct quantifiable measurement of the return to the organization for the investment in IMS. We have included discussion not only on the technical merits of IMS study conduct but also the key elements of setting study objectives, building collaborations, data integration into the medicine progression milestones, and potential pitfalls when trying to establish IMS in the pharmaceutical arena. We categorized IMS study types into five groups that parallel pipeline progression from the earliest phases of discovery to late stages of preclinical development. We conclude the article with some perspectives on how we see MALDI IMS maintaining relevance and becoming further embedded as an essential tool in the constantly changing environment of the pharmaceutical industry.