Direct Molecular Analysis of Whole-Body Animal Tissue Sections by Imaging MALDI Mass Spectrometry

TLDR

Imaging mass spectrometry using MALDI enables a label‑free, spatially resolved molecular view of resected organs or whole‑body animal sections, tracking endogenous and exogenous compounds with high specificity. The method extends whole‑body MALDI IMS to detect proteins across entire sagittal tissue sections. The study shows that whole‑body MALDI IMS can simultaneously map drug and metabolite distributions over time—olanzapine and its metabolites in rats matched autoradiography data—and indicates its potential to advance therapeutic and toxicological analysis by revealing molecular causes of efficacy and side effects.

Abstract

Imaging mass spectrometry (IMS) that utilizes matrix-assisted laser desorption/ionization (MALDI) technology can provide a molecular ex vivo view of resected organs or whole-body sections from an animal, making possible the label-free tracking of both endogenous and exogenous compounds with spatial resolution and molecular specificity. Drug distribution and, for the first time, individual metabolite distributions within whole-body tissue sections can be detected simultaneously at various time points following drug administration. IMS analysis of tissues from 8 mg/kg olanzapine dosed rats revealed temporal distribution of the drug and metabolites that correlate to previous quantitative whole-body autoradiography studies. Whole-body MALDI IMS is further extended to detecting proteins from organs present in a whole-body sagittal tissue section. This technology will significantly help advance the analysis of novel therapeutics and may provide deeper insight into therapeutic and toxicological processes, revealing at the molecular level the cause of efficacy or side effects often associated with drug administration.