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Quantitative distribution studies in animals: cross-validation of radioluminography versus liquid-scintillation
W Steinke1, Y Archimbaud, M Becka
1Preclinical Pharmacokinetics, Bayer AG, D-42096 Wuppertal, Germany. wolfram.steinke.ws@bayer-ag.de
Abstract:
The results of a cross-validation of the radioluminography (RLG) and liquid scintillation counting (LSC) methods are presented. The methods for the determination of radioactivity concentrations were compared in 16 organs, after administration of (14)C-labeled substances to rats. LSC measurements of two kinds were used as reference methods for RLG: (1) quantitative determination of radioactivity after conventional dissection (interindividual comparison) and (2) quantitative determination of radioactivity in tissue punches taken from the whole-body sections after they had undergone RLG measurement (intraindividual comparison). Blood standards containing known concentrations were used for calibration. For statistical evaluation log-linear regression analysis of paired concentration values and organ-specific 95% confidence intervals of the log-transformed RLG/LSC concentration quotients were compared. For most organs, the slopes of the regression lines and the means of the concentration quotients were within the defined equivalence range of 0.80-1.25. Deviations were distinctly smaller in the intraindividual comparison. For some organs, however, it became clear that found concentrations were affected by self-absorption (RLG) and by differences in sample preparation (LSC). In conclusion, quantification with RLG is a reliable and reproducible method with comparable measurement precision and greater accuracy in respect of tissue localization, compared to LSC (dissection).