A NOVEL QUANTITATIVE METHOD FOR DETERMINING THE BIODISTRIBUTION OF RADIOLABELED XENOBIOTICS USING WHOLE-BODY CRYOSECTIONING AND AUTORADIOLUMINOGRAPHY

A novel method is described for quantitative whole-body autoradiolumin ography using [C-14]-radioactive standards prepared from rat red blood cells. MicroComputer Imaging Device model 2 (MCID) and ImageQuant (IQ ) imaging systems were evaluated for imaging performance and autoradio luminography quantitation. Weighted linear regression analysis resulte d in linearity over five orders of magnitude with a lower limit of qua ntitation of 2.7 nCi/g. Using IQ, 16 days were necessary for image ana lysis and data processing of 30 whole-body cryosections and 1080 stand ards. MCID reduced the image and data processing of the same cryosecti ons and standards to only 4 days. Embedding a series of radioactive st andards with each specimen in the same carboxymethyl cellulose block p rovided an effective method of assessing intrasection and intersection variations in thickness of whole-body cryosections. These results dem onstrated that autoradioluminography provided a sensitive, accurate, p recise and reproducible method for the quantitative measurement of the tissue distribution of [C-14]-radiolabeled xenobiotics in whole-body cryosections. Evaluating the biodistribution of [C-14]-xenobiotics by autoradioluminography, not only provides pharmacokinetic data required for predicting the potential tissue deposition of an absorbed dose of radioactivity in man, but also allows for visual and quantitative eva luation of radioactivity in small anatomical structures that otherwise could not be detected or measured by conventional tissue combustion t echnology.