Radioactivity in tissues

The pattern of distribution of the absorbed radioactivity is shewn in Figure 1. After 6 hrs of exposure the concentration of radioactivity was highest in gall bladder and intestine and the radioactivity was distributed in most tissues except brain and heart after 24 hr. Twenty-four hrs after transfer to fresh water (24+24), most of the radioactivity in tissues had disappeared... 

Table III summarizes the results of tissue residue analysis. It is evident that the amount of radioactivity in tissues was not directly related to the length of chemical exposure. The average accumulation in fish exposed from 1 to 14 days was 1.35%. In general, liver, kidney, intestine, and bile contained the most 1 C. C-labeled materials accumulated in the liver at levels 3 to 5 times greater than [111C]molinate concentration in the water. The maximum radiocarbon level in the bile was 14.5 ppm and was reached by the 7th day. On the 14th day, the radiocarbon decreased to 6.09 ppm which was 30-fold higher than the [ 1 C]molinate water concentration. Blood contained negligible amounts of radioactivity, and little of that was associated with the plasma. Twenty percent of total blood radioactivity was detected in the erythrocytes within 4 days after treatment and by the 14th day, 69% of the radiocarbon in whole blood was present in the erythrocytes.

Radioactivity distribution. The N-hexane lipido/sterolic extract (LSESr) supplemented with [ C]-labeled oleic or lauric acids or P-sitosterol was administered orally to rats. The highest level of radioactivity uptake was LSESr supplemented with [ C]-labeled oleic acid. Ratios of radioactivity in tissues compared to plasma showed an uptake of radioactivity greater in prostate as compared with other genital organs, i.e., the seminal vesicles or to other organs such as... 

Figure 1. Percent of initial radioactivity in tissues of Crassastrea gigas during...

The specific activity in plasma was found to be higher than that in tissues, therefore the total turnover derived from plasma is lower than the turnover derived from radioactivity in tissues. 

Repeated exposure of mice and rats to 1,1,1-thchloroethane apparently does not increase the relative importance of metabolism to the in vivo disposition of the compound (Schumann et al. 1982b), even though another research group reported that hepatic microsomes from rats exposed continuously for 10 days to 800 ppm of 1,1,1 -trichloroethane displayed greater in vitro enzymatic activities for 1,1,1-thchloroethane oxidation than microsomes from fresh-air controls (Koizumi et al. 1983). Schumann et al. (1982b) found that repeated exposure of rats or mice to 1,500 ppm unlabeled 1,1,1-thchloroethane for 16 months did not alter the routes of excretion, the extent of metabolism, or the concentration of radioactivity in tissues after a 6-hour inhalation exposure to... 

Following administration of a carrier/DN A complex to animals, plasmid can be quantified as described above. The distribution, half-life, and other pharmacokinetic parameters of the plasmid can then be calculated if recovery is adequate. The simplest method to follow DNA in vivo is to utilize radiolabeled DNA and to assess radioactivity in tissue homogenates after transfection (39,121-123). One must be careful to account for the total dose in order to make analysis of the data meaningful. Upon systemic administration, for example, larger organs, such as the liver, may take up more of the total dose, but may not account for the largest proportion when normalized to tissue weight (124). 

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],... 

Figure 7b. Concentration of total radioactivity in tissue after oral administration 42 mg/kg) of " C- or S-sulfadimethoxine to lobsters Homarus americanus) (n = 4-6).

Autoradiography is particularly well suited for determining the distribution of radioactivity in tissue. In principle, the distribution of radioactivity in a tissue could be assessed by gas flow counting, if the tissue was dissected, its parts weighed and uniformly spread as a dry film on a degassed planchet. However, very often it is difficult to identify exactly the part of the tissue that has been dissected. Furthermore, the fluids which surround the tissue in the body may often be very highly labelled and will contaminate the dissected specimen. The use of autoradiography readily overcomes these difficulties . 

The distribution of radioactivity in tissues and intestinal contents one hour after administration of 8a-[S-(N-acetyl)-L-cysteinyl]-D-[l- C]riboflavin is summarized in Table 2. That at least the flavinyl moiety must be absorbed from the gastrointestinal tract was indicated by the rapid and sequential appearance of a fraction of in those tissues, such as liver, that similarly reflect the uptake of [2- C]riboflavin. The rather rapid appearance of in kidney, especially after i.p. injection, was also typical for flavin localization and preceded excretion of a considerable fraction of the label. The considerable radioactivity in the small intestine and its contents after i.p., as well as per os, administration reflects entero-hepatic circulation. Only traces of 002 were exhaled within even... 

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