Tissue radioactivity

Plasma levels of 3—5 p.g/mL are obtained two hours after adraiinistration of 200 mg ketoconazole. No accumulation in the bloodstream was noted after a 30-wk treatment with this dose. The half-life is approximately eight hours. When ketoconazole is taken with meals, higher plasma levels are obtained. Distribution studies using radioactive ketoconazole in rats show radioactivity mainly in the Hver and the connective tissue. Radioactivity is also present in the subcutaneous tissue and the sebaceous glands. After one dose of 200 mg in humans, ketoconazole is found in urine, saUva, sebum, and cenimen. Like miconazole, the mode of action is based on inhibition of the cytochrome P-450 dependent biosynthesis of ergosterol. This results in disturbed membrane permeabiUty and membrane-bound enzymes (8,10,23,25). 

The uptake of TRA into cervical tissue was determined by measuring tissue radioactivity following insertion of the collagen sponge cervical cap containing tritium-labeled TRA. The TRA concentrations peaked at 4 hr and then diminished rapidly by 24 hr. Since measurements of blood samples revealed that no systemic absorption had occurred, high local concentrations over an extended period of time may be possible without systemic side effects. 

Arukwe et al. [15] dosed Atlantic salmon with radioactive labeled NP. Fish were frozen immediately until gall bladder, skin, kidney, gill, liver, muscle, fat, remaining carcass and viscera were sampled and analysed. Tissue radioactivity was analysed by liquid scintillation counting after combustion of aliquots in an oxidiser apparatus. Metabolites (biliary and urinary) were separated by radio-HPLC. 

Devices incorporating animal-derived tissues, radioactive materials, in vitro diagnostics and devices manufactured in other countries, such as the United States (even those devices that have CE marking) are excluded. 

Following single daily intravenous injections of radiolabeled flunixin in cattle at the rate of 2.2 mg/kg bw for 3 consecutive days, the parent compound accounted for 50% of the extractable tissue radioactivity, composing the major residue in liver and kidney (94). Three metabolites were also present in both liver and kidney samples 4-hydroxyflunixin was present at higher levels, whereas 5-hydroxyflunixin and 2-methylhydroxyflunixin occurred at lower levels. 

Studies of the distribution of [3H]ginsenoside Rgl following intravenous injection have been performed in mice (80). Tissue radioactivity was greatest in the kidney, followed by the adrenal gland, liver, lungs, spleen, pancreas, heart, testes, and brain. Plasma protein binding was 24%, and tissue protein binding was 48% in the liver, 22% in testes, and 8% in the brain. 

Radloiodlne Treatment Radioiodine therapy is particularly well-suited for the treatment of autonomously functioning thyroid tissue. Radioactive iodine, like the natural element, is taken up by the thyroid gland via an active process (the sodium iodide symporter) and accumulates within the thyroid gland. The therapeutic effect occurs as a result of tissue destruction (radiation thyroiditis) caused by short-reached (3 radiation detection is enabled due to emission of a small portion of irradiation. The radioactive material is selectively trapped by the more active autonomously functioning cells and, to a lesser extent, by normal thyrocytes, which depend on TSH stimulation to increase iodine uptake. 

When used at doses that defiver 150 Gy or more (<150p,Gi I/g of thyroid tissue), radioactive iodine is an effective cure for Graves disease and is associated with few acute side-effects. Potential long-term adverse side-effects, including thyroid cancer and genetic damage, have yet to be observed in individuals treated as children or adolescents with 1. 

For data presentation, tissue radioactivity levels are expressed as nanogram-equivalents per gram tissue (Table 18.Al), and tissue/plasma ratios. The maximum concentration (Cmax) and the time to reach maximum concentration (Fmax) are obtained by visual inspection of the raw data. Pharmacokinetic parameters, included half-life (fi/2), area under the concentration-time curve... 

Olabeled compounds 2 laCi/mL for H-labeled compounds) for 30 min. Thereafter the material is transferred to a superfusion apparatus (Cutler et al., 1971) and superfused with nonradioactive solution. The effluent is collected into continuously changing vials. At the end of the superfusion period, both the radioactivity of the collection vials and the residual radioactivity in the tissue are determined. The initial content of labeled solute in the slices is obtained from the sum of residual tissue radioactivity and effluent radioactivity, and is expressed as 100%. The percentage of labeled solute remaining in the tissue at any time is calculated by subtracting the cumulative radioactivity recovered in the effluent from the initial tissue content (see Fig. 2 for an efflux time course). 

Fig. 3.2. A lAA flux into basal agar receivers from 10-mm sections of corn coleoptiles apically supplied with a 5-min pulse of " C-IAA (5 pM in agar). At the time indicated by each column, the sections (30 per transport block) were transferred to new receivers. (Data from Hertel and Flory 1968). B Distribution of mobile auxin in oat coleoptiles apically supplied with a 10-min pulse of " C-IAA (0.7 pM in agar). The mobile auxin concentration was estimated from the radioactivity in basal agar receivers taken from samples of nine coleoptiles subdivided serially into 1-mm sections at the times measured from the start of donor application. Note the differences in translocation of the peak, indicated by arrows, in different regions of the coleoptile. (Data from Newman 1970). C Distribution of radioactivity within 20-mm sections of corn coleoptiles apically supplied with a 15-min pulse of C-IAA (10 pM in agar). The pulse donors were replaced by blocks containing unlabeled lAA at an identical concentration. The sections were cut into successive 2-mm pieces at the times indicated, and the level of tissue radioactivity was measured. Note the differences in translocation of the peak, indicated by arrows, during the two 30-min transport periods. (Data from Goldsmith 1967b)...

These platforms include planar gamma scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). They differ in their availability, cost, need for specialized infrastructure and technical expertise, and ability to accurately quantify tissue radioactivity noninvasively (9). 

The accuracy of tissue radioactivity measurements with PET, however, makes it possible to use potentially more robust methods of quantitation. For instance, a commonly used method of quantifying tracers that are irreversibly trapped within tissues (at least during the scan) is to calculate a so-called net influx rate constant, Ki. An example of a reporter protein that functions this... 

Fig. 3. Effect of estrogen on uptake of uridine-Tl by the uterus and its incorporation into acid-insoluble material and nuclear RNA. The data are expressed as percent of control value. Brackets show the ranges of triplicate experiments. Five uteri were pooled for each experimental or control group. The control values are 6920 cpm/mg homogenate DNA 11.0% acid-insoluble radioactivity and 1204 cpm/mg nuclear RNA. For each period of time tested for estrogen action, separate control experiments were performed. Thus the control values given here at time zero for tissue radioactivity and nuclear RNA specific activity, and for acid-insoluble radioactivity represent, respectively, the mean for 15 control groups (i.e., three for each time period of estrogen action tested). From Means and Hamilton (1966).

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