MALDI mass spectrometric imaging of biological tissue sections.

ABSTRACT

In biomedical research, the discovery of new biomarkers and new drugs demands analytical techniques with high sensitivity together with increased throughput. The possibility to localize or to follow changes in organisms at the molecular level by imaging component distributions of specific tissues, is of prime importance to unravel biochemical pathways and develop new treatments and drugs. Established molecular imaging techniques such as MRI and PET are already widely used, however their need for molecular probes to report the presence of the analytes of interest precludes the simultaneous exploration of different biomolecules. Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) takes full advantage of the high sensitivity of mass spectrometry instrumentation but also of the ability of the latter to simultaneously detect a wide range of compounds, almost regardless from their nature and mass. To perform MALDI MSI, sections of biological tissues are introduced in an MALDI MS instrument, where the UV pulsed laser of the MALDI source is used to raster over a selected area while acquiring mass spectra of the ablated ions at every image point. From this array of spectra, hundreds of analyte-specific images can be generated based on the selected masses. MALDI MSI can be used to track biomarkers such as peptides or proteins but also to map drug/tissue interactions. In this paper, an overview of the possibilities of MSI will be given. As an example, MSI on brain tissue sections for the study of Alzheimer's disease (AD) will be shown. Mapping of amyloid peptides as a new approach for drug lead optimization will be presented. Target identification thanks to MSI will be introduced and the last part will be dedicated to the molecular scanner approach, which gives access to high-mass range by combining tissue blotting and digestion in a one-step process.