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Medical Specializations


Pathology => Anatomy => Isotopic Tracer


Isotopic Tracer


INTRODUCTION
Isotopic Tracer, name applied to an atom of an isotope used to observe the movement of certain materials in chemical, biological, or physical processes. The term tracer is applied commonly to any radioactive isotope employed in tracing the course of nonradioactive substances. In scientific usage, however, the term is applied also to less abundant nonradioactive, or stable, isotopes that are suitable for use in tracer techniques.

Tracers may be used to follow the movement of substances in large or small amounts as well as at molecular or atomic levels. The observations may be made by the measurement of radioactivity in the case of radioactive tracers, or of the relative abundance of isotopes in applications employing stable isotopes as tracers. Instruments used to detect radiation include the electroscope, the scintillation counter, and the Geiger-Müller counter . In investigations using stable isotopes as tracers, the instrument most commonly employed is the mass spectrometer, a device that can determine the relative amounts of various isotopes in a sample of the substance being analyzed. Tracers have important applications in many fields of scientific research and in medicine, agriculture, and industry.

BULK-MATERIAL TRACING
Although the movement of large masses of solids or fluids may be studied by many diverse methods, including visual observation of tracer dyes, the use of radioactive tracers in bulk-material applications offers such advantages as greater speed of operation, reliability, and convenience. For example, radioactive tracers may be used to mark the boundary between different grades of oil flowing in a pipeline by injecting at the juncture of two types of oil a radioactive material that emits penetrating gamma rays. Radiation detectors placed in the pipeline will detect the gamma rays as this interface passes a given point. The detectors can then be made to operate valves that channel the two grades of oil into different outlets.

Tracers are used in industry to detect microscopic amounts of wear. The lubricating quality of an oil, for example, can be evaluated after prolonged operation in an experimental engine by measuring the amount of wear on piston rings and cylinder walls and by the amount of steel deposits in the oil. Such experiments are time consuming and difficult to apply on a routine basis. In the tracer technique, the piston rings are made radioactive by exposing them to neutrons in a nuclear reactor . After the engine has been operating for a relatively short period, radioactive material worn from the piston ring can be detected in the oil and walls of the cylinder, and the amount of this material serves as an index for evaluating the quality of the oil.

Radioactive tracers may also be used to control the transfer of dyes in multicolor textile printing. Color-printing machines consist of several rollers, each furnished with a dye bath of a different color. One color may be carried over by the fabric from one roller to the next, thus producing so-called color soiling of the textiles. If such soiling is not discovered in time, hundreds of yards of valuable fabric may be spoiled. One method of avoiding spoilage is frequent replacement of the dye solutions. To eliminate the necessity for this costly procedure, the offending, or pirate, color is labeled by adding radioactive phosphate to the dye bath. Contamination of subsequent dye baths with the pirate color is monitored by radiation detectors, which are dipped automatically into the solutions at frequent intervals. When the pirate color reaches a critical concentration, the dye bath is replaced by a fresh one.

TRACING OF MOLECULES AND ATOMS
Most substances are compounds consisting of molecules linked together in chemical combination or are mixtures of compounds. Only one type of molecule in a compound may be of importance in a particular tracer application. Important also, especially in biochemical research, is the ability to distinguish within a single compound similar molecules derived from two different sources. This information can be made available by the use of the technique called isotopic labeling.

Tracers are used in botanic and agricultural research to study the absorption of nutrients by plants and to trace metabolic pathways, especially those involved in photosynthesis.

In biological research, molecules labeled with radioactive isotopes have been especially useful in elucidating the metabolic pathways of biochemical synthesis and degradation. The routes of many nutrients and toxins through ecosystems have also been mapped by tracer techniques.

Tracer procedures are used in medical diagnosis and research to measure such functions of organs and tissues as their uptake of hormones, minerals, vitamins, blood or blood components, and drugs. Organ output of hormones or other proteins and wastes can also be measured with great speed and accuracy.

CHEMICAL RESEARCH
Procedures of tracing, labeling, and double labeling are of greatest significance in biochemical research, permitting the investigator to follow the paths of breakdown and formation of normal components of the body. The use of such procedures had made it possible to trace the origin of each atom in a complicated molecule such as the heme pigment of hemoglobin, which has the formula Fe(C32H30N4) (COOH)2. The carbon atoms have been shown to come from the precursor acetic acid CH3COOH, which contains two groups, each with one carbon atom. In addition, by double labeling it is possible to determine which of the carbon atoms in the heme pigment come from the COOH group of the acetic acid molecule and which come from the CH3 group. The nitrogen in the heme-pigment molecule is derived from the intermediate compound aminoacetic acid.

In organic-chemical research, tracers have been used to investigate many chemical reactions involving the migration and rearrangement of atoms and groups of atoms. Labeling and double-labeling procedures have demonstrated the mechanism of some obscure and complicated reactions and have revealed that presumedly simple reactions were often more involved.

In inorganic chemistry, tracers have made possible the study of systems in which no net chemical reaction occurs but in which, for example, two oxidation states of the same element are present. Tracer techniques have shown that, without net chemical reaction, an interchange of atoms takes place between such forms in a system as divalent cobalt and trivalent cobalt or as ferrocyanide and ferricyanide. Such interchanges, which are known as exchange reactions, are a logical extension of the chemical principle of dynamic equilibrium.

CHOICE OF TRACERS
For elements having only one stable isotope, no other stable-isotope tracer is available; all tracers used to investigate these elements must be the radioactive forms. For studies involving certain other elements, the only radioactive isotopes obtainable have such an extremely short half-life as to render them useless; in this case the tracers must be low-abundance stable isotopes prepared in enriched form. The tracing of stable isotopes depends on observing the deviations from normal isotopic mass ratios using the mass spectrograph. Particle detectors are used to measure radioactive tracers.
In some studies, a choice may be available between stable-isotope tracers and radioactive-isotope tracers-for example, between the two carbon isotopes stable carbon-13 and radioactive carbon-14 or between the two hydrogen isotopes stable deuterium (hydrogen-2) and radioactive tritium (hydrogen-3). If both types of measuring instruments (mass spectrograph and radiation-measuring equipment) are available, selection of the tracer is governed by the so-called dilution factor, which is a measure of the concentration of tracer material required for detection. Generally, radioactive tracers may be detected in much smaller quantities than stable tracers. For example, carbon-13 constitutes 1.108 percent of natural carbon, and a change of 0.001 percent in its abundance may be detected readily. In other words, a pure carbon-13 tracer would be detectable after being diluted 100,000 to 1 million times with natural carbon-12. Thus, if a sugar (glucose) molecule were labeled with a pure carbon-13 isotope, the tracer could be detected only in experiments involving not more than 100,000 to 1 million times as many unlabeled carbon atoms.

Radioactive carbon-14, however, can be detected at concentrations of about 25 disintegrations per minute in a carbon sample weighing 1 g. Based on the rate of disintegration of pure carbon-14, which has a half-life of about 5760 years, the amount of detectable carbon-14 in the carbon sample is about 0.04 parts per 1 billion, corresponding to a dilution factor of 25 billion. Because the material is radioactive, however, safety considerations usually impose a practical upper limit to the concentration that may be used experimentally. Although deuterium is not radioactive, similar considerations lead to dilution limits of about 1 million for deuterium and 10 trillion for tritium. Deuterium affects living tissue because it is twice as heavy as ordinary hydrogen. Nevertheless, small laboratory animals have survived when 20 to 30 percent of their body fluid, experimentally, consisted of heavy water (D2O).

PREPARATION OF TRACERS
Availability of stable isotopic tracers depends on isotope-separation procedures and on natural abundances. In principle, all isotope separations can be made by an instrument working on the mass-spectrograph principle. Certain isotopes may be separated by gaseous-diffusion processes, as in the case of uranium, and by multiple distillation procedures, as in the case of hydrogen . The most practical separation procedures involve repetitive isotope-exchange reactions, as a result of which heavy and light isotopes are separated from each other. Most deuterium, carbon-13, and nitrogen-15 isotope preparations are produced in this manner.

Radioactive tracers are generally prepared by neutron bombardment of the stable element, which captures the neutrons to form the heavier isotopes that decay by emitting beta particles. For example, in the preparation of carbon-14, the next-heavier element, in this instance, nitrogen, is bombarded with neutrons because the captured neutron causes ejection of a proton, thus forming the radioactive isotope of the element with the next-lower atomic number.

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