Radiolabeled molecules

Because of concerns about the safety of radioisotope use, researchers are developing fluorescent and chemiluminescent methods for detection of small amounts of biomolecules on gels. One attractive approach is to label biomolecules before analysis with the coenzyme biotin. Biotin forms a strong complex with enzyme-linked streptavidin. Some dynamic property of the enzyme is then measured to locate the biotin-labeled biomolecule on the gel. These new methods approach the sensitivity of methods involving radiolabeled molecules, and rapid advances are being made. 

As a branch of chemistry, the activities of nuclear chemists frequentiy span several traditional areas of chemistry such as organic, analytical, inorganic, and physical chemistry. Nuclear chemistry has ties to all branches of chemistry. For example, nuclear chemists are frequently involved with the synthesis and preparation of radiolabeled molecules for use in research or medicine. Nuclear analytical techniques are an important part of the arsenal of the modem analytical chemist. The study of the actinide and transactinide elements has involved the joint efforts of nuclear and inorganic chemists in extending knowledge of the periodic table. Certainly, the physical concepts and reasoning at the heart of modem nuclear chemistry are familiar to physical chemists. In this book we will touch on many of these interdisciplinary topics and attempt to bring in familiar chemical concepts. 

The responses are typically initiated by the specific interaction of the environmentally encountered chemical with receptors that are deployed on the cell surface. Radiolabeled biotin, for example, interacts with a structurally selective receptor with an estimated affinity (as represented by the KD) of 400 pM this compares with a behavioral EC50 for this substance of 300 pM. Compounds that are structurally similar to biotin can compete for the binding of the radiolabeled molecule, whereas compounds that are structurally different cannot. 

The availability of an on-line radioisotope detector for CE is especially appealing for several reasons. First, state-of-the-art radiation detection technology offers extremely high sensitivity. Second, radioisotope detection affords unrivaled selectivity because only radiolabeled sample components yield a response at the detector. Third, the radiolabeled molecule possesses the same chemical properties as the un-labeled molecule, thereby permitting tracer studies. Fourth, radioisotope detection can be directly calibrated to provide a measurement of absolute concentration of the labeled species. Finally, a capillary electrophoresis system in which radioactivity detection is coupled with more conventional detectors adds extra versatility to this new separation technique. 

Since radiolabeled molecules are hazardous and difficult to dispose, most researchers and clinical laboratories prefer to use nonisotopic methods of labeling molecules. For this reason, investigators have established (3-glucosidase assay conditions that allow the estimation of glucocerebrosidase content of human tissues when nonphysiological (3-glucosides serve as the substrate. The artificial substrate of choice,... 

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 . 

For the past two decades, there has been considerable interest in the use of short lived, moderate energy, beta emitting radionuclides for targeted radionuclide therapy [12.1-12.3]. This therapy involves the use of a radiolabelled molecule to selectively dehver a cytotoxic level of radiation to a diseased site with maximum radiation dose to the tumour and minimum radiation dose to normal organs. A number of beta particle emitting radionuchdes such as Lu, Sm and Ho are available for targeted radionuchde therapy for a wide range of tissues. The physical characteristics of these radionuchdes are listed in Table 12.1. 

Trace the following radiolabeled molecule through the biosynthetic route to AMP synthesis. 

A sensitive method for tracking a protein or other biological molecule is by detecting the radioactivity emitted from radioisotopes introduced into the molecule. At least one atom in a radiolabeled molecule is present in a radioactive form, called a radioisotope. 

Labeling Experiments and Detection of Radiolabeled Molecules Whether labeled compounds are detected by autoradiography, a semlquantltatlve visual assay, or their radio activity is measured in an appropriate counter, a highly quantitative assay that can determine the concentration of a radiolabeled compound in a sample, depends on the nature of the experiment. In some experiments, both types of detection are used. 

A wide variety of radiolabeled molecules have been used for the scintigraphic detection of inflammation or infection foci. Iodine-labeled molecules include antibodies or cytokines. 

Radioactive elements, especially carbon-14, were key products of the Manhattan Project, and could be produced in large quantities by the nuclear reactors. They would provide the world with new tools for chemical and biomedical research. Radioactive tracers were able to broadcast their presence as part of radiolabeled molecules as they defined the the stream of life. Being able to measure the chemical processes in every part of the body of living organisms made it possible for creative biological and medical scientists to provide a whole new approach to biochemistry and medicine. The radionuclides, chiefly carbon-14 and phosphorus-32, led the way. 

Investigations utilizing tritiated molecules are fraught with numerous methodological problems. Most significant among these are the exchange of tritium between radiolabeled molecules and water and the subsequent loss of tritiated water vapor into the atmosphere (for example see Jacobs,... 

PET/microPET Radiolabeled molecules Couple of y-rays emitted by annihilation of emitted positrons from radionuclides l-2mm Minute- hours Deep Examine the chemical activity in certain parts of the body in case of caiKxr, heart disease, brain disorders... 

SPECT Radiolabeled molecules Emitted y-tays l-2mm Minute- hours Deep Reveal how tisoes [Pg.366]

Targeted radionuclide therapy involves the use of a radiolabeled molecule to selectively deliver a cytotoxic level of radiation to a disease site. The overriding objectives of radionuclide therapy and external beam therapy are the same obtaining the maximum radiation dose for the tumor while minimizing the irradiation of normal organs. However, the two treatment approaches differ considerably with regard to the impediments that must be overcome to achieve this goal. 

Radiolabeled molecules should be synthesized so that the labeled atom is located as close to the photolabile group as possible, and should not be separated from it by any linkages that might be cleaved during subsequent manipulations. 

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