Radioactive concentration

Kinetics of the biodistribution must be compatible with the practical aspects of hospital routine and imaging capabiUty. In the case of a diagnostic agent, maximal lesion contrast, maximal radioactivity concentrations in tissue of interest, and minimal background radioactivity during the time imaging... 

Single-photon emission computed tomography (SPECT) studies are acquired by rotating the y-camera around the patient s long axis. These data are then used to reconstmct the radioactivity distribution in three dimensions. This may be displayed as sHces of radioactivity concentration or rendered so as to present the appearance of a soHd volume. 

FIGURE 3.3 Displacement of prebound radioligand [A ] by non-radioactive concentrations of [A]. Curve for a= 1 denotes no cooperativity in binding (i.e., formation of the receptor dimer does not lead to a change in the affinity of the receptor for either [A] or [A ]). The curve a= 10 indicates a system whereby formation of the receptor dimer leads to a tenfold increase in the affinity for both [A ] and [A], In this case, it can be seen that addition on the nonradioactive ligand [A] actually leads to an increase in the amount of radioligand [A ] bound before a decrease at higher concentrations of [A], For this simulation [A ]/Kd = 0.1. 

Radon and its decay products were a major focus of meetings held in Capri, Italy, in 1983 and in Maastricht, the Netherlands, in 1985. These meetings reported on ongoing national surveys in European countries, on laboratory and field studies on the properties of radon decay products, and on the models for relating the airborne radioactivity concentrations to the human lung. 

Data are not corrected for physical decay and are listed in approximate order of decreasing radioactivity concentrations. h Tissue weights were normalized to a total body weight of 10 kg. c L.N. indicates Lymph Nodes. 

Radiolabeled studies in rats demonstrated highest exposure to radioactivity from an i.v. C-brinzolamide dose in tissues containing high CA concentrations. These included liver, kidneys, spleen, lungs and salivary glands. Radioactivity concentrations in fat, nerve, skeletal muscle, skin, eyes and testes were low. Experiments in pregnant and lactating rats demonstrated transfer of radioactivity across the placental barrier and secretion of low concentrations in milk. 

The results for total radioactive concentration C = Ci + C% at 5 cm depth are given in Figure E2.8.2. The estimates indicate that at z = 5 cm, the maximum concentration will be 2.35x10 ° g/m at 15 years after the spUl. For these conditions, the state does not need to increase the thickness of the cap. 

Carrier-free 125I, radioactive concentration 100 mCi/mL (e.g., code IMS.30, Amersham International, Amersham, UK)... 

Cameron and Patrick (1966) generally confirmed their own autoradiography results quantitatively. At 48-hours post-dosing, data showed the same distribution of radioactivity for both perfused and unperfused tissue samples. A comparison of radioactivity concentration between blood and other tissues was not possible, since the... 

Fig. 4.4 Tissue distribution of total radioactivity at 24 h after single IV bolus administration of5 mg/kg [3H]-labeled ISIS 104838 or ISIS 113715 to rats. Concentration values represent total radioactivity concentration in microgram equivalent/g (pg eq/g).

The reconstructed images reflect counts per volume or radioactivity concentrations. The data are converted to SUV images based on the following formula (12). 

SUV provides an easy approach to obtain distribution values in order to compare the results from different PET examinations or patient studies. SUV has no dimension and is related to the increased or decreased accumulation of the tracer in a local region, as compared to the average radioactivity concentration based on the individual dose and body weight. Usually SUV measured 55-60 min post-injection is used for the analysis of tracer studies. 

The use of radiolabeled molecules allows a drug and its labeled metabolites to be followed throughout the body and excreta over time. The radioactivity concentration can be tracked in blood and plasma as well as in tissues. Whether the drug with its specific radioactivity administered to the body is completely captured can be proven by calculating the so-called mass balance . 

Whereas the radioactivity measurement alone does not allow distinguishing between drug and metabo-lite(s), samples obtained from the described studies should be also used for standard determination of the drug and its known metabolites, receiving information about the drag and the known metabolite kinetics directly. The gap between radioactivity concentrations and the concentrations determined by direct bioana-lytical methods defines the contribution of unknown metabolites. 

OF THE RADIOACTIVITY CONCENTRATION Radioactivity measurements are carried out by the liquid scintillation counting procedure in -spectrometers using an external standard device which permitted the counting efficiency to be determined by the channel ratio method (explained for instance by Dyer (1980)). 

A thorough calibration of the ((-spectrometer regarding different sample matrices and sizes, the scintillator used, different dissolutions, different colorations of the samples, different amounts of CO2 after combustion and of course different radioactivity concentrations should be ensured. Calibration and control samples can be set up by using internal standard kits (for instance 14C-0 Standard from PerkinElmer Wallac GmbH D-79111 Freiburg). 

For small animals or dosing of a large number of animals, individual doses are determined by weighing the syringes containing the galenic formulation prior to and after each administration stability of radioactive concentration is determined on two aliquots before and after each series of administration. 

To evaluate the pattern and the rate of excretion and to investigate the time course of radioactivity concentrations in blood and plasma with the aim of getting information about the absorption process, the AUC, Cmax and the elimination half-life of radioactivity in blood and plasma. Possibly, indices for enterohepatic... 

Always keep in mind that the radioactivity represents the sum of the original compound and/or radiolabeled metabolites and not the drug itself. Therefore, it is worthwhile to determine also the drug and known metabolites directly by bioanalytical methods with samples withdrawn from the same study. The comparison of both, the radioactivity concentrations and the sum of concentrations determined by specific methods, allows estimation of the gap (of unknown metabolites) which often develops time-dependently for instance at the beginning of the study radioactivity concentrations in plasma should fit to the drug concentration. Usually, the gap (as a percentage of the total radioactivity at a certain time point) between both concentrations increases with time. 

AVE 3559 was developed for the treatment of obe-sitas. It was 14C-labeled and investigated in a dog radiokinetic study to determine the time course of radioactivity concentrations in blood/plasma and to determine the pattern and rate of excretion, the residual concentrations at the end of the study 168 h after administration and the mass balance following oral and intravenous route of administration. 

Already 15 minutes after oral administration mean radioactivity concentrations of 5.60 ig equivalents/g (range 3.9 to 7.4 pig equivalents/g) and 8.47 xg equivalents/g (range 5.8 to 11.1 pig equivalents/g), respectively, were present in blood and plasma indicating... 

Already 15 min after oral administration, radioactivity concentrations in blood and plasma (5.90 and 10.67 ig equivalents/g, resp.) were found indicating a fast absorption. The maximum concentrations (Cmax) occurred 0.5 hours after administration and amounted to a mean of 9.34 pg equivalents/g (blood) and 16.95 pg equivalents/g (plasma). The elimination of radioactivity from blood and plasma was biphasic. The half-lives for the first phase amounted to 1.1 h (blood) and 0.9 h (plasma), for the second phase half-lives of 7.5 h and 6.3 h were calculated. In all animals, radioactivity concentrations were detectable up to the last measuring time 48 h after dosing and showed averages of 0.025 and 0.024 pg equivalents/g (blood and plasma, respectively). 

After intravenous administration, the maximum radioactivity concentrations were measured at the first measuring time 5 min after administration, exhibiting mean concentrations of 4.79 and 7.64 xg equivalents/g (blood and plasma). Following the peak values, the radioactivity decreased in a biphasic process with mean half-lives of 0.4 h for phase I and 10 h (blood and plasma, resp.) for phase II. In all animals, blood and plasma levels were observed up to 48 h after administration (0.006 and 0.007 xg equivalents/g in blood and plasma, resp.)... 

Since all plasma radioactivity concentrations are distinctly higher than the corresponding blood values, there is no indication for a major binding of radioactivity to formed blood elements in this study. 

Parts of the non-diluted bile obtained are pooled in order to receive a representative mixture of metabolites on one hand (that is from different collection intervals) and on the other hand a radioactivity concentration as high as possible. 

A rough estimation whether anesthesia might relevantly misrepresent the situation of an awake animal should be performed comparing the bile excretion with the excretion via feces from the mass balance study (see example), the urine excretion or the radioactivity concentration in blood (so the bile fistula study should be extended to collect also body fluids such as terminal blood or the urine during the anesthesia). 

Examinations are performed concerning the radioactivity concentrations and portions. 

The radioactivity concentrations in the collected samples are determined. They are expressed in ig equivalents of drug/g and in % of administered radioactivity. The temporal course of the concentrations and the portions of radioactivity found can be represented by graph and tables. In cases where mean portions of administered radioactivity of a tissue/body fluid of all three time points are distributed about a single straight line in a semi logarithmic plot (In concentrations on time), the rate constant can be calculated by linear regression and subsequently the half-life (ln2/rate constant). 

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