Imaging mass spectrometry for visualization of drug and endogenous metabolite distribution: toward in situ pharmacometabolomes.

摘要

It is important to determine how a candidate drug is distributed and metabolized within the body in early phase of drug discovery. Recently, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS; also referred to as mass spectrometry imaging) has attracted great interest for monitoring drug delivery and metabolism. Since this emerging technique enables simultaneous imaging of many types of metabolite molecules, MALDI-IMS can visualize and distinguish the parent drug and its metabolites. As another important advantage, changes in endogenous metabolites in response to drug administration can be mapped and evaluated in tissue sections. In this review, we discuss the capabilities of current IMS techniques for imaging metabolite molecules and summarize representative studies on imaging of both endogenous and exogenous metabolites. In addition, current limitations and problems with the technique are discussed, and reports of progress toward solving these problems are summarized. With this new tool, the pharmacological research community can begin to map the in situ pharmacometabolome.