Progressive application of autoradiography in pharmacokinetic and metabolic studies for the development of new drugs.

Autoradiographic data of distinctive tissue distributions of 14C atoms obtained by labeling at two different positions of a new drug suggest the metabolic fates of each labeled compound in experimental animals. A more accurate determination of blood-brain barrier (BBB) damage in several regions was indicated by semimicroautoradioluminography, based on no passage of dopamine through the BBB. Autoradioluminography (ARLG) was useful for quantitative validation of whole body autoradiography (WBA) with both ordinal X-ray film and other detectors. In frozen specimens, a good correlation was obtained between the relative radioactivity, photostimulated luminescence (PSL), and liquid scintillation counting (LSC) values in each organ or tissue. However, the correlation was disturbed in lung, brain, bone, and adipose tissue after freeze-drying. In order to be listed in the regulatory items, WBA data must be quantitative as well. The paste-mold method presented here can be used to support WBA data. The thin-layer chromatography (TLC)-ARLG technique and its applications are also presented in this article. A blood concentration-time curve of both the parent compound and its unknown metabolites can be estimated with this technique.