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 autoradioluminography using [14C]-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 autoradioluminography quantitation. Weighted linear regression analysis resulted in linearity over five orders of magnitude with a lower limit of quantitation of 2.7 nCi/g. Using IQ, 16 days were necessary for image analysis and data processing of 30 whole-body cryosections and 1080 standards. MCID reduced the image and data processing of the same cryosections and standards to only 4 days. Embedding a series of radioactive standards with each specimen in the same carboxymethyl cellulose block provided an effective method of assessing intrasection and intersection variations in thickness of whole-body cryosections. These results demonstrated that autoradioluminography provided a sensitive, accurate, precise and reproducible method for the quantitative measurement of the tissue distribution of [14C]-radiolabeled xenobiotics in whole-body cryosections. Evaluating the biodistribution of [14C]-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 evaluation of radioactivity in small anatomical structures that otherwise could not be detected or measured by conventional tissue combustion technology.
Pfizer Inc, Central Research, Department of Drug Metabolism, Groton, Connecticut.
M J
MJ
Potchoiba
T G
TG
Tensfeldt
M R
MR
Nocerini
B M
BM
Silber
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D016616:Cryoultramicrotomy; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015262:Xenobiotics / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D015262:Xenobiotics