Imaging Plate: Validation and First Experience with Quantitative Studies in Whole-Body Autoradiography during Drug Development

Abstract

The imaging plate technique (radioluminography, RLG) is a fascinating new tool in whole-body autoradiography (WBAR). While being a standard technique for the qualitative evaluation of the distribution of new drugs for many years, WBAR has some major drawbacks preventing its broader use for quantitative studies (time consuming, difficult to standardize, very limited linearity, low sensitivity). Most of these problems are now solved by RLG, thus offering the possibility to perform also quantitative distribution studies with autoradiographic methods (QWBAR). However, before using RLG during drug development, a careful validation of the method has to be done. Crucial points are linearity for concentration and exposure time, reproducibility, as well as stability of information and resolution. Influences of exposure temperature, shielding, and imaging plate handling have to be standardized. By the use of internal standards and correction for selfabsorption in different tissues, calibration was performed and compared to a tissue dissection study. It is concluded that the RLG is a real break through from the scientific point of view. It clearly will replace WBAR with X-ray film for carbon-14. For its quantitative use, RLG may combine the advantages of WBAR (high resolution, completeness of the distribution pattern) and the quantitative distribution studies (concentrations, accumulation factors, time course of elimination from organs and tissues). However, scientific and economic aspects have to be carefully evaluated before replacing the quantitative distribution studies as a whole by QWBAR. To date only a selective use of the RLG for the evaluation of accumulation in substructures, placental transfer studies, and urgent issues during drug development can be proposed.