Quantitative whole-body

Ahmed, A.E., Jacob, S. Loh, J.P. (1991) Studies on the mechanism of haloacetonitriles toxicity quantitative whole body autoradiographic distribution of [2-i4C]chloroacetonitrile in rats. Toxicology, 67,279-302... 

The data are finally drawn together for detailed discussion and evaluation with special attention to known results from other radiokinetic studies such as the mass balance study and the obtained fecal elimination or the quantitative whole body autoradiography. 

Instead of the described procedure of a common quantitative distribution study, the placental transfer can be investigated nicely also by quantitative whole body autoradiography (see the section on autoradiography and for instance Endo et al. (1992) or Suwelack et al. (1985)). The quantitative whole body autoradiography was extended also for the use of pregnant rabbits (Herman 1998). 

Quantitative Whole-Body Autoradiography (QWBA) is based on the RLG technique and the use of standards obtained from dilution series containing known concentrations of radioactivity. Isotopes used in QWBA are mainly 14C and 3H. These standards were cut together with the whole-body sections to ensure an identical thickness and used for the internal calibration. The information of the calibration curve allows the determination of the concentrations in the organs and tissues of interest which can be derived from the measured area and the section thickness. 

Distribution studies with radiolabeled test substances in animals are an important part of the drug development process. Routine methods used for these studies are quantitative whole-body autoradiography (QWBA) and alternatively quantitative tissue distribution studies (QTD) with dissection of the animals and measurement of radioactivity in pre-selected organs and tissues using a liquid scintillation counter. 

To save animals and time, the quantitative tissue distribution study is more and more replaced by the quantitative whole-body autoradiography. 

The majority of the 14C-human ADME studies are conducted with a small number of healthy adult subjects (often between 6-8) and if bile collection is needed, a small group of additional subjects are included [228], Traditionally, due to ethical reasons, male subjects are selected for the 14C-ADME studies. Before the start of the 14C-ADME studies, study sponsors have the responsibility to determine stability of the radiolabel, purity of the radiolabel (distinguishing degradants from metabolites is very important), and conduct tissue distribution studies in nonclinical species preferably using quantitative whole-body autoradiography (QWBA) to detect radioactivity in tissues, organs, and excreta to determine the safe radioactivity dose. Nonclinical tissue distribution study data are extrapolated and used to show that radioactivity exposure of a specific tissue/organ will be well below the allowable limits to humans [229,230], Most of the 14C-human ADME studies consider a total radioactivity dose of 100[tCi or less to be safe [231],... 

Li, Q. et al., The distribution pattern of intravenous [(14)C] artesunate in rat tissues by quantitative whole-body autoradiography and tissue dissection techniques, J. Pharm. Biomed. Anal., 48(3), 876, 2008. 

Richter, W.F., Starke, V., and Whitby, B., The distribution pattern of radioactivity across different tissues in quantitative whole-body autoradiography (QWBA) studies, Eur. J. Pharm. Sci., 28(1-2), 155, 2006. 

Solon, E.G. and Kraus, L., Quantitative whole-body autoradiography in the pharmaceutical industry Survey results on study design, methods, and regulatory compliance, J. Pharmacol. Toxicol., 46, 73, 2002. 

Coe, R.A.J., Quantitative whole-body autoradiography, Regul. Toxicol. Pharm., 31, SI, 2000. 

Anger KS, Aigner S, Biihler M, et al. 1980. [Quantitative whole-body bone scintigraphy. II. Pharmacokinetics of osteotropic radiopharmaceuticals]. Nuklearmedizin 19(3) 97-107. (German)... 

Tissue distribution studies in pigmented Long-Evans rats to provide dosimetry to various tissues and organs are required to support human ADME with radiolabeled compound. Typically, these studies are limited to a single dose by the intended route of administration (PO, IV, etc.). The radioactivity levels in various tissues at different time points can be measured by quantitative whole-body autoradiography (QWBA) where sections of the... 

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