Clinical radiometry

Clinical radiometry is the measurement of the radioactivity of the whole body or part of it after the introduction of a radiopharmaceutical into the body. Usually, gamma-emitting radionuclides are used in clinical practice. After the introduction of a radiopharmaceutical containing such a radionuclide into the body, its radiation is captured by a scintillation detector located above the corresponding part of the patient's body. The results of the study are usually presented on a light board as the number of pulses registered over a certain period of time, or as a count rate (in pulses per minute). In clinical practice, this method is not of great importance. It is usually used in cases where it is necessary to identify and evaluate the incorporation of radionuclides when they accidentally enter the human body - through carelessness, in disasters.

A more interesting method is whole-body radiometry. During this method, a person is placed in a special low-background chamber containing several specially oriented scintillation detectors. This allows recording radioactive radiation from the whole body, and under conditions of minimal influence of the natural radioactive background, which, as is known, can be quite high in some areas of the Earth's surface. If during radiometry any part of the body (organ) is covered with a lead plate, then the contribution of this part of the body (or the organ located under the plate) to the overall radioactivity of the body can be assessed. In this way, it is possible to study the metabolism of proteins, vitamins, iron, and determine the volume of extracellular water. This method is also used in examining people with accidental incorporation of radionuclides (instead of conventional clinical radiometry).

Automated radiometers are used for laboratory radiometry. They have test tubes with radioactive material on a conveyor. Under the control of a microprocessor, the test tubes are automatically fed to the well counter window; after radiometry is completed, the test tubes are automatically changed. The measurement results are calculated in a computer, and after appropriate processing, they are sent to a printing device. Modern radiometers perform complex calculations automatically, and the doctor receives ready information, for example, about the concentration of hormones and enzymes in the blood, indicating the accuracy of the measurements taken. If the volume of work on laboratory radiometry is small, then simpler radiometers are used with manual movement of test tubes and manual radiometry, in a non-automatic mode.

Radionuclide diagnostics in vitro (from the Latin vitrum - glass, since all studies are carried out in test tubes) refers to microanalysis and occupies a borderline position between radiology and clinical biochemistry. It allows detecting the presence of various substances of endogenous and exogenous origin in biological fluids (blood, urine), which are there in negligible or, as chemists say, disappearing concentrations. Such substances include hormones, enzymes, drugs introduced into the body for therapeutic purposes, etc.

In various diseases, such as cancer or myocardial infarction, substances specific to these diseases appear in the body. They are called markers (from the English mark). The concentration of markers is as negligible as that of hormones: literally single molecules in 1 ml of blood.

All these studies, unique in their accuracy, can be carried out using radioimmunological analysis, developed in 1960 by American researchers S. Berson and R. Yalow, who were subsequently awarded the Nobel Prize for this work. Its wide implementation in clinical practice marked a revolutionary leap in microanalysis and radionuclide diagnostics. For the first time, doctors received the opportunity, and a very real one, to decipher the mechanisms of development of many diseases and diagnose them at the earliest stages. Endocrinologists, therapists, obstetricians, and pediatricians felt the importance of the new method most visibly.

The principle of the radioimmunological method consists of competitive binding of the desired stable and similar labeled substances with a specific receptor system.

To perform such an analysis, standard sets of reagents are produced, each of which is designed to determine the concentration of a particular substance.

As can be seen in the figure, the binding system (usually specific antibodies or antiserum) interacts simultaneously with two antigens, one of which is the desired one, the other is its labeled analogue. Solutions are used in which the labeled antigen always contains more than antibodies. In this case, a real struggle between the labeled and unlabeled antigens for the connection with antibodies is played out. The latter belong to immunoglobulins of class G.

They must be highly specific, i.e. react only with the antigen being studied. Antibodies accept only specific antigens at their open binding sites, and in quantities proportional to the number of antigens. This mechanism is figuratively described as the "lock and key" phenomenon: the greater the initial content of the desired antigen in the reacting solutions, the less radioactive analogue of the antigen will be captured by the binding system and the greater its portion will remain unbound.

Simultaneously with the determination of the concentration of the desired substance in the patient's blood, under the same conditions and with the same reagents, a study of standard sera with a precisely determined concentration of the desired antigen is carried out. Based on the ratio of the radioactivities of the reacted components, a calibration curve is constructed, reflecting the dependence of the sample radioactivity on the concentration of the substance being studied. Then, by comparing the radioactivity of the samples of material obtained from the patient with the calibration curve, the concentration of the desired substance in the sample is determined.

Radionuclide in vitro analysis began to be called radioimmunological, since it is based on the use of immunological reactions antigen-antibody. However, other types of in vitro studies were created later, similar in purpose and methodology, but differing in details. Thus, if an antibody is used as a labeled substance, and not an antigen, the analysis is called immunoradiometric; if tissue receptors are used as a binding system, they speak of radioreceptor analysis.

The in vitro radionuclide study consists of 4 stages.

• The first stage is mixing the analyzed biological sample with reagents from the kit containing antiserum (antibodies) and a binding system. All manipulations with solutions are carried out using special semi-automatic micropipettes, in some laboratories they are carried out using machines.
• The second stage is incubation of the mixture. It continues until dynamic equilibrium is reached: depending on the specificity of the antigen, its duration varies from several minutes to several hours and even days.
• The third stage is the separation of free and bound radioactive substances. For this purpose, the sorbents available in the kit (ion exchange resins, carbon, etc.) are used, precipitating heavier antigen-antibody complexes.
• The fourth stage is radiometry of samples, construction of calibration curves, determination of the concentration of the desired substance. All these works are performed automatically using a radiometer equipped with a microprocessor and a printer.

As can be seen from the above, radioimmunological analysis is based on the use of a radioactive antigen label. However, in principle, other substances can be used as an antigen or antibody label, in particular enzymes, luminophores or highly fluorescent molecules. This is the basis for new microanalysis methods: immunoenzyme, immunoluminescent, immunofluorescent. Some of them are very promising and compete with radioimmunological research.

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