Autoradiography, Imaging Mass Spectrometry and Other Preclinical Imaging Techniques to Study Tissue Distribution of Xenobiotics in Animal Models

The determination of the absorption, pharmacokinetics, distribution, metabolism, and elimination (ADME) characteristics of new small and large molecule therapeutic entities plays a major role in the drug discovery and development processes. Combinations of new and old detection systems in drug research has advanced the discovery and development small molecule drugs and biotherapeutics. The data obtained from micro-autoradiography (MARG), quantitative whole-body autoradiography (QWBA), cryo-imaging, and imaging mass spectrometry (IMS) can be coupled with in vivo imaging data to offer high resolution answers to numerous questions regarding ADME properties of therapeutic compounds, such as: organ-tissue-cellular localization, receptor-specific localization, subcellular localization, drug interactions, gene expression, formulation comparisons, nanoparticle tracking, stem cell migration, virus localization, tissue metabolite ID, pharmacokinetics, pharmacodynamics, and target organ/tumor penetration. These techniques have been used to quantitatively assess the ADME characteristics of small molecule drugs, radiopharmaceuticals, proteins, peptides, oligonucleotides, antibodies, anti-body drug conjugates, and siRNA. A brief description of ADME study designs, the state-of-the-arts, and examples of their applications will be presented here.