RADIO PHARMACEUTICALS (RFP) — diagnostic or the remedies containing radioactive nuclides. Diagnostic radio pharmaceuticals use for the purpose of studying of an anatomo-topographical state or assessment of function of various bodies and systems of an organism. Effect of therapeutic radio pharmaceuticals on patol, process is caused unlike usual pharmaceuticals biol, a radiation effect of radionuclide (see. Isotopes ).
Suggested to use radiotracers for scientific research in 1913 D. Hevesha. In 1927 H. L. Blumgart and S. Weiss for the first time used radioactive material — radon (see) — with the diagnostic purpose for determination of speed of a blood-groove. Systematically began to apply radionuclides in medicine from 40th 20 century.
Properties of radio pharmaceutical drug are defined by physical properties of radionuclide and chemical connection, on a basis to-rogo it is created. The main at the choice of radionuclide are the characteristic of its radiation (energy and an exit of γ-quanta, half-life), and also opportunities and conditions of receiving. Half-life of radionuclide (see Half-life) defines the exposure dose of the patient created by RFP and a possibility of use of drug for a specific research along with other factors. According to Wagner (N. of N. Wagner, 1966), the chosen radionuclide shall have the half-life equal to ln21t where t — time of a research after introduction of RFP. In this case a ratio between conditions of obtaining information at a radio isotope research and an exposure dose of the patient optimum. Since the size of an absorbed dose consists of all types of radiation, radionuclides with the minimum exit of the radiation which is not used for registration are preferable to diagnostic testings. As techniques of a research are based by hl. obr. on registration of γ-quanta or characteristic x-ray emission, in the best way it is provided during the use of the radionuclides which are breaking up by isomeric transition (see the Isomerism, atomic kernels). The limit of energy of γ-radiation, equal 100 — 200 kev is optimum. At lower values of energy absorption by its fabrics increases. With increase in energy efficiency of registration of radiation the detector decreases and collimation becomes complicated (see). The ideal radionuclide used for creation of diagnostic RFP shall possess the following main characteristics: 1) one line of γ-quanta; 2) radiation energy 100 — 200 kev; 3) type of disintegration in the form of isomeric transition or electron capture; 4) the half-life which is not differing considerably from duration of a research.
The radionuclide used in therapeutic RFP usually possesses not gamma, but beta radiation, it gives the chance to concentrate its action in a zone patol, the center at the minimum damage of surrounding fabrics.
Chemical connection (the main substance), on a basis to-rogo is created by RFP, defines it biol, behavior in an organism: time of accumulation and a delay in specific body, the speed of its removal from body and an organism. Functional suitability as which understand a possibility of use of RFP for this radio diagnostic test or a possibility of therapeutic use is defined by these indicators. For giving of RFP of necessary nature of distribution use various fiziol, and biochemical, mechanisms, to basic of which belong participation in metabolic processes, phagocytosis, diffusion, physical. - chemical adsorption, sequestration of cells, temporary capillary blockade, localization in a certain area of an organism, reaction antigen — an antibody and enzyme — substrate. In certain cases the mechanism providing this or that nature of distribution of RFP remains not found out. For therapeutic RFP such chemical properties which can provide selective accumulation of drug only in patol, the center are optimum.
The special group is made by the diagnostic RFP containing the short-lived radionuclides received from generators. The generator represents system of genetically connected two radionuclides — long-living maternal and short-lived affiliated. Disintegration of the first of them leads to education of the second. The generator includes the column containing this or that sorbent with the adsorbed maternal radionuclide and system of communications for release of affiliated radionuclide. Most generating systems were widely used 99 Mo — 99m Tc and 113 Sn — 113m In. Introduction in the mid-sixties in a wedge, practice 99mTc was of great importance, nuclear and physical characteristics to-rogo do it almost ideal for many radio diagnostic methods. Use of the drugs containing ultrashort-lived radionuclides develops ( 11 With, 13 N, 15 O), received on cyclotrons. At the same time use various inorganic compounds, e.g. 11 CO, 11 CO 2 , 13 NH 3 , 15 O 2 , H 2 15 O, 13 N 2 , 15 CO 2 , and also marked amino acids, sugar, steroids, etc. These radionuclides break up with an exit of positrons and formation of two pair γ-quanta scattering at an angle 180 ° that creates ideal conditions for emission tomography.
Quality control and quantitative characteristics of RFP are established by the relevant national commissions (in the USSR — Pharmacopoeian committee M3 of the USSR). By production of RFP apply various control methods: physical (definition of radionuclide purity, volume and specific activity), chemical (establishment of radiochemical and chemical purity) and biological (definition of sterility and apirogennost).
Radionuclide purity is the share of the general activity of drug caused by necessary radionuclide. Radionuclide impurity can raise an exposure dose of the patient, reduce accuracy and distort results of a research. Volume activity — it the content of radionuclide is 1 ml of drug; is established taking into account a method of use and a shelf-life of RFP. Specific activity — the content of radionuclide in a weight unit (weight) of the main substance; is defined by possible influence of quantity of the last on biol, behavior of drug and its pharmacological (toxic) properties. These three parameters control by means of radiometry (see) and spectrometry.
Radiochemical purity — a share of the radionuclide which is in RFP in a necessary chemical form. E.g., if radiochemical purity 131 I-gippurana makes 98%, it means that 98% 131 I in drug is connected with gippurany. Radiochemical impurity can affect reliability of the obtained information considerably. In particular, for definition of an effective blood-groove of kidneys it can be used 131 I-gippuran with radiochemical purity is not lower than 98%. Chemical purity of drug is defined by availability in it of foreign, not labeled chemical substances. Special attention is paid in this case to impurity of heavy metals. Control of radiochemical and chemical purity is carried out by means of a chromatography (see), by spektrofotometriya (see), an issue spectral analysis (see), etc.
Use of diagnostic RFP is based on the principle of radionuclide indication of chemical connections. Inclusion in structure of chemical compound of radionuclide does not change its properties, gives the chance to monitor distribution of RFP in an organism by outside registration of radiation. Thus, radionuclides allow to study directly physiological and biochemical, processes, without breaking their natural course that is essentially important advantage of radionuclide diagnosis. Its main techniques are constructed on the principle of isotope cultivation (scoping of the circulating blood, plasma and erythrocytes, water content in an organism, etc.), on registration of distribution of RFP in body or system (see. Scanning ,, Stsintigrafiya ), determination of size of its accumulation in body or the center of defeat (diagnosis of a functional condition of a thyroid gland with 131 I, tumors — with 32 P), registration of kinetics of RFP in body or fabric — a renografiya (see Renografiya radio isotope), gepatografiya, definition of a fabric blood-groove and removal of RFP from an organism (diagnosis of disturbance of absorption of fats in went. - kish. path). The list of diagnostic RFP, the main methods of a research at which they are used ways of introduction and the main properties is provided in table 1.
Use of therapeutic RFP is based on destruction of fabrics patol. the center by their radiation. The main problem at the same time is concentration of RFP in a zone patol, the center that is reached or its selection absorption, or, e.g., by introduction directly to the center. In table 2 the list of therapeutic RFP, the main indications is provided to their use, ways of introduction and amount of the administered drug.
Use of RFP is inevitably connected with beam load of an organism of the patient that theoretically represents potentiality of somatic damages or genetic effects. Calculation of values of risk is difficult in connection with very small in some cases volume of the direct data obtained for the person by means of which it is possible to prove estimates and therefore the majority of calculations is based on extrapolation of risk at high doses. The fabric exposure doses created at diagnostic use by RFP in most cases make the 100-th and tenth shares is glad. In the Soviet Union the approved M3 of the USSR «Standards of radiation safety for patients during the use of radioactive materials with the diagnostic purpose», regulating admissibility of this or that radio diagnostic procedure depending on a research objective work. diseases, age of the patient and the created exposure doses. Reduction of an exposure dose to such minimum level which provides satisfactory results of a research shall be the rule. Use of RFP is contraindicated at pregnant women and the nursing women, in certain cases — at children up to 16 years. Besides, some RFP have separate contraindications.
Use of RFP is admissible only in special radio diagnostic departments with observance of measures of radiation safety as concerning medical staff, and the environment (see. Antiactinic protection ). The complex of radiation and hygienic actions in the USSR is regulated by special legislative documents — «Standard of Radiation Safety» (SRS) and «The ground health regulations of work with radioactive materials and other sources ionizing izlucheny».
The main side effects at use of RFP — the pyrogenic and allergic reactions, an idiosyncrasy (see). Their frequency, according to different researchers, fluctuates in very wide limits — from 0,4% to 15%.
Bibliography: Levin V. I. Receiving radioisotopes, M., 1972; Parker R., Smith P. and Taylor D. Bases of a nuclear medicine, the lane with English, M., 1981; A t k i n s H. L. Radiopharmaceuti-cals, Physics reports, v. 21c, p. 315, 1975; BlumgartH. La. Weiss S. Studies on the velocity of the blood flow, J. clin. Invest., v. 4, p. 15, 1927.
G. A. Zubovsky, H. F. Tarasov.