Radiolabeled substances from

Figure 2. Effect of 1 (xM AFM on efflux of various radiolabeled substances from cucumber cotyledons ( ). At time zero, cotyledons were exposed to 600 fiE/m s (PAR) light and herbicide. A, Efflux of Cl. B, Efflux of C, Efflux of...

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

Mucociliary clearance can be studied in vivo in humans using gamma scintigraphy to follow the clearance of radiolabeled solutions from the nasal cavity or by measuring the transport rate of radiolabeled markers administered to the nasal epithelium. Simpler methods are used to monitor the appearance of a strongly colored dye (by visual inspection) or sweet tasting substance such as saccharin (by taste) at the pharyngeal cavity. 

As the radiolabeled substances emerge from the laboratory to the clinics, there will be a need for scaling up the batch size of the product. This can be done by increasing either the total volume of the produced batches or the specific activity of the product or both. When doing this, the following aspects should be considered ... 

Together with details of sample preparation and storage, an appropriate analytical method of known accuracy, precision, and sensitivity must be available for the quantification of the substance in the test solution and in the biological material. If these are lacking it is impossible to determine a true BCF. The use of radiolabelled test substance can facilitate the analysis of water and fish samples. However, unless combined with a specific analytical method, the total radioactivity measurements potentially reflect the presence of parent substance, possible metabolite(s), and possible metabolized carbon, which have been incorporated in the fish tissue in organic molecules. For the determination of a true BCF it is essential to clearly discriminate the parent substance from possible metabolites. If radiolabelled materials are used in the test, it is possible to analyse for total radio label (i.e. parent and metabolites) or the samples may be purified so that the parent compound can be analysed separately. 

Radiation therapy The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monodonal antibody, that circulates throughout the body. Also called radiotherapy, [nih]... 

Since the glucose-lysine reaction mixture used in this study consisted of a number of different substances, it was of interest to study whether the observed inhibitory effect in vitro could be attributed to some specific compound(s). In order to obtain a separation, an aliquot of the LMW fraction, radiolabel led by [U- glucose added to the reactants, was applied on a Sephadex G-50 column and eluted with water. The UV absorbance was recorded and the eluate was collected in fractions. The degree of inhibition effected by small samples of equal volume from each fraction and exerted on carboxypeptidase A and purified aminopeptidase N was determined as well as the radioactivity... 

When a radiolabeled form of the analyte is available, the amount in the wash and sample elution steps is easily measured, thereby facilitating optimum development. Other analytical techniques can be used, although care must be taken to avoid interference from the sample matrix. The ability of IAC to separate analyte from interferences can be assessed through either LC or GC determination for small molecule determination or SDS-PAGE for large molecule determination where co-elution of other substances can be easily observed. 

This paper is the only one in the liquid chromatography portion of this symposium which will attempt to deal with chromatography specifically from the viewpoint of the pesticide metabolism chemist. A residue analyst knows what compound he must analyze for, and develops his method with the properties of that substance in mind. On the other hand, the pesticide metabolism chemist has a different problem. At the conclusion of the treatment, exposure, and harvest phases of a radiolabeled metabolism study, he divides his material into appropriate samples, and extracts each sample with selected solvents to obtain the radioactive materials in soluble form. Typically these extracts consist of low levels (ppm) of carbon-14 labeled metabolites in a complicated mixture of normal natural products from the plant, animal, or soil source. The identity of each metabolite is unknown, and each must be isolated from the natural background and from other labeled metabolites in sufficient quantity and in adequate purity for identification studies, usually by mass spectrometry. The situation is rather like looking for the proverbial "needle in the haystack" when one does not know the size, shape,or composition of the needle, or even how many needles there are in the stack. At this point a separation technique must be selected with certain important requirements in mind. 

To measure the transport of drugs across the BBB in vitro 2.5 iCi of 3H-labelled drug and 14C-sucrose are applied to each Transwell (in case of 14C-labeled substances, permeability studies are performed with 3H-sucrose). This concentration is high enough to ensure sufficient excess to neglect the decrease of tracer in the donor (apical) compartment during the experiments. Volumes of 1.5 ml in the donor (apical) and 2.5 ml in the acceptor (basolateral) compartment avoid hydrostatic pressure. After addition of the radiolabeled compound, samples of 50 til are taken in duplicate from the basolateral acceptor compartment every 20 min and replaced by 100 xl of fresh assay medium. Cells are kept under culture conditions during the whole transport experiment. Radioactivity is measured after addition of liquid scintillation cocktail in a counter. 

Additionally, before the first study with radiolabeled test substance in man can be started, a risk assessment of a human radiokinetic study is mandatory. The estimation of the radiation exposure in humans given a radiolabeled dose is based on exposure data obtained typically from QWBA studies in animals. 

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