Quantitative Imaging Using Autoradiographic Techniques

Autoradiography (ARG) is a powerful, high resolution, quantitative molecular imaging technique used to study the tissue distribution of radiolabeled xenobiotics in biological models. ARG involves the close apposition of solid specimens containing radiolabeled substance to a detector layer, such as photographic emulsions, film, phosphor imaging plates, and direct nuclear imagers/counters and the two basic types include: Macro-autoradiography, which is imaging of organs, organ systems, and/or whole-body sections (WBA); and micro-autoradiography (MARG), which provides localization of radioactivity at the cellular level. The basic technique is more than 60 years, but it remained largely qualitative due to the limited linear range of quantification offered by nuclear emulsion detection systems. However, recent technologies have revolutionized the techniques of WBA and made quantification of radioactivity in tissues possible. WBA and MARG techniques provide drug researchers with quantitative tissue concentration data and a high resolution visual location of those drug or biologic concentrations in intact organs, tissues, and cells of laboratory animals. In addition, novel techniques such as matrix-assisted laser desorption imaging mass spectrometry (MALDI-MSI), and Secondary Ion Mass Spectrometric (SIMS) imaging can positively identify the molecular identity and image the spatial distribution of the parent drug and/or their metabolites in the same samples used for whole-body and micro-autoradiography. This chapter presents an overview of the techniques and reviews the use of QWBA, MARG, MALDI-MS, SIMS, and tissue extraction and liquid chromatography/mass spectroscopy (LC/MS) in the pharmaceutical industry.