The isotopes of the elements that are heavier than mercury are all part of the radio­active decay series except At-211, which is produced in cyclotrons. The half-life of At-211 is 7.21 h, and it has alpha radiation. In addition, Pb-201 is produced from Tl-203 (Eq. (8.27)).

8.6.21 Transuranium Elements

The production of transuranium elements was discussed in Section 6.2.6.

Radioactive isotopes and their radiation have many uses in analytical chemistry. The procedures involving them can be divided into two groups. The procedures in the first group are based on the principle that radioactive isotopes have the same chemical properties as the stable isotopes of the same element (here, the isotope effects are ignored). These analytical methods employ radioactive isotopes called tracers (see Section 10.1).

The second group of the analytical applications of radioactivity includes the methods in which the samples are irradiated by particles or electromagnetic radia­tion, and the impacts of these radiations on the matter or the change in the proper­ties of the irradiating particles or photons are studied. This means that analytical and structural information are obtained via studying the interactions of radiation with matter (see Section 10.2).

Batch mixing of solid granular substances or materials of other consistencies is one of the most frequently applied technological operations in this industry. Although a homogenization process depends on several parameters (physical features of the substance, type of mixer, and operation mode), the most frequent question is how
long a mixture in the applied mixer must be mixed to achieve the required homogeneity.

To answer this question, one component of the mixture is labeled with a radio­active tracer prior to the study. The labeled component is placed in the mixing equipment in accordance with the normal technological process and the mixing process is launched. Depending on the required information (e. g., if homogeneity is needed to describe with a quantitative metric number or only information on the sufficient homogenization time is needed to achieve the best homogeneity which cannot be improved with longer mixing), sampling or an outer detection technique is applied.

For sampling, the mixing process is suspended in certain time intervals and a statistically sufficient number of samples are taken from the mixture, followed by measuring the count rates of the samples and the statistical processing of the count rates. The mixture homogeneity is determined by calculating the relative standard deviation of the sample counts:

where a is the count rate of a sample, a is the average of the counts, and n is the serial number of the sample.

By plotting the obtained relative standard deviation values as a function of time, the optimal homogenization time (where homogeneity does not change further) can be determined (as shown in Figure 11.7).

When applying the outer detection technique (Figure 11.8), the detector(s) are installed outside the mixing equipment wall, which will follow movement of the radioactive tracer and concentration equalization of the mixture. The time change of the detector signal does not provide quantitative information on the homogeneity of the mixture; it only shows how much time is needed for the equali­zation (for ending the signal fluctuation). The outer detector technique requires

approximately 10 times more activity than the sampling technique, but it is much faster and it is a noninvasive method.

Most of the homogenization studies have been performed in Hungary in the field of porcelain manufacturing and cement production using fluidization raw meal mixers.

Examples for homogization studies carried out with radiotracer technique include:

• Homogenization of components (Co and W metal powder) of hard metal production.

• Homogenization of components of porcelain mixture with labeling a powder fraction.

• Homogenization of a wet porcelain mixture with labeling the wetting agent.

• Study of the raw meal fluidization type homogenization in cement factories (with Au-198 colloid tracer).

We generally process the data representing the distribution of radiopharmaceuticals with the help of computers. Computers are applied to achieve the following:

12.4.4.1 Enhancing Image Quality

When images are recorded directly to film, depending on the brightness setting of the oscilloscope, they may be over — or underexposed and that cannot be corrected afterward. On the contrary, digitized images allow the best possible contrast in any subarea to be selected by using different color or grayscale palettes.

Image filtering may be applied to suppress the noise and thus enhance the signal-to-noise ratio.

Chemical dosimeters utilize the chemical effects of radiation. In fact, autoradiogra­phy (see Section 14.5.2) also works in this way. In addition, thermoluminescence

detectors are mentioned: they absorb and store the energy of the radiation at room temperature, and then, after heating to 200—300°C, they emit the energy as lumi­nescent (light) photons. The thermoluminenscence detectors are made of calcium sulfate and lithium fluoride doped with dysprosium.

Bi-210 has been separated on nickel plate by electrolysis, and then bismuth sulfide has been prepared. This has been used for the radioactive indicator of proteins.

8.5.1.2 Po-210

Po-210 has been used for the preparation of alpha radiation sources.

From the members of the decay series of Th-232 (see Figure 4.6), Ra-228, Th-228, Rn-220, and Pb-212 isotopes have been used as radioactive indicators. Since these are the isotopes of the same elements as the members of the decay series of U-238, the applications are also similar. An emanation source can be pro­duced from Th-228, from which Rn-220, and its daughter nuclide, Pb-212 can be separated electrostatically (see Figure 8.6) and applied as radioactive indicators. The electrostatic separation is based on the recoil of the daughter nucleus when emitting the alpha particle (as discussed in Section 4.4.1). As a result of the recoil, the daughter nuclide is ionized; the positive ions can be collected electrostatically on the negative electrode.

In Table 8.3, the quantities of radioactive isotopes in secular equilibrium in 1 g uranium-238, uranium-235, and thorium-232 isotopes are shown. These are the upper limits of the quantities of isotopes that can be obtained from 1 g of uranium and thorium isotopes. According to the natural isotopic ratio of uranium, 1 ton of uranium contains 993 kg of 238U and 3 kg of 235U. In addition, the uranium and thorium concentration of the rocks is also very small (<0.1%). These data illustrate that the separation of the natural radioactive isotopes is very difficult.

— Electrode holder

— Electric insulation

■ Wall of the tank (positively charged)

Pt electrode (negatively charged)

Th-228 precipitated onto iron(III) oxide

Figure 8.6 Electrostatic separation of daughter elements of Th-228.

The facilities and equipment for producing radioactive preparations (generally

representing high activities) must fulfill three conditions simultaneously:

• protection against radiation of the radioactive material (e. g., radiation protection for employees),

• protection against radioactive contamination (e. g., protection of the surrounding area from radioactive contamination and prevention of incorporation of radioactive materials in human organs),

• protection against microbiological contamination (e. g., avoiding infection of the product caused by bacteria and fungi); this third type of protection relates to radiopharmaceuticals only.

Testing Method

With ion-chamber dose calibrator.

A smear test is made on the surface of the sealed radiation source, and activity on the sponge is detected.

The sealed radiation source is soaked in a solvent in which solubility of the radiation source (pellet) is good but that of the capsule is low. The activity of the solvent is then measured.

The sealed radiation source is placed into ethylene glycol, the vessel is vacuumed, and the appearance of bubbling is observed.

Protection against radiation depends on the type of radiation IAEA Safety Series No.1 (1973). As most radioactive products emit gamma radiation, which has the highest range, the highest level of protection is against gamma radiation. The effi­cient protection against gamma radiation is the application of absorbing shielding walls made of high-density materials (lead, heavy concrete, etc.). However, against

pure beta radiation, which is free of gammas, shielding material is made of ele­ments of low atomic number (e. g., plexi).

In radioactive isotope processing facilities, monitoring systems indicating the level of radiation are installed, and personnel are supplied with personal dosimeters.

So-called hot cells, which are separated from their surroundings by shielded walls and equipped with manipulators provide protection against radioactive con­tamination of the surrounding area and prevention from incorporation in humans (e. g., introduction of radioactive materials into the human body, mainly by inhala­tion). From hot cells, the air is continuously exhausted and led to chimneys through filters. Shielding walls serve not only to separate the space from its surrounding but also for radiation protection by absorbing radiation (Figure 8.14). Simultaneously, fresh air is continuously introduced into the surrounding area by ventilators which, together with the exhaustion, provide the necessary pressure differences, forcing the air flow from potentially less-contaminated areas toward potentially contami­nated areas (e. g., from dressing rooms toward the working area, and then toward the hot cells and the chimney).

Facilities serving for handling radioactive materials are classified into “A,” “B,” and “C” radiation protection categories depending on the harm and activity of the handled radioactive material. Facilities processing high activities classified in cate­gory A are equipped with series of hot cells and are separated from the surrounding areas by dressing rooms.

The third type of protection, namely protecting the product from microbiological contamination, requires the opposite air flow direction than that is applied against radioactive contamination. Because airborne particles are typical carriers for bacte­ria and mainly responsible for dissemination, a filtered air flow free of bacteria is introduced into the area around the product in the direction of the outside area (such systems are called “clean rooms” in the traditional pharmaceutical manufac­ture). In addition to controlling air flow conditions, working surfaces need to be regularly disinfected, which in closed hot cells is not easy to do. In addition to

Figure 8.14 A hot cell system equipped with radiation­shielding walls.

these protections, operators executing production are also microbiological contami­nation sources; for this reason, special protection clothing is necessary.

Consequently, radioactive contamination protection requires manufacturing areas with negative pressure (Figure 8.14), while microbiological protection requires areas with positive pressure (Figure 8.15).

Due to the opposite requirements relating to the air flow and considering requirements for radiation protection, radioactive materials in the pharmaceutical grade are manufactured in facilities that combine the two systems. Such combined systems are radioactive hot cells installed in aseptic clean rooms, where filtered air from the clean room is introduced into the hot cells or alternatively, hot cells with controlled internal air supply—so-called negative pressure isolators—where filtered air with a lower flow rate is introduced into the hot cell, while air with a higher flow rate is extracted from the hot cell. The difference between the air flow rate of the inlet and outlet guarantees that negative pressure is required for radioactive contamination protection within the hot cell. The introduction of filtered air and the maintenance of negative pressure provide simultaneous protection against microbi­ological and radioactive contamination in the same space.

The protocol to satisfy the requirements of radiation protection, protection against radioactive contamination, and protection against microbiological contami­nation is not completely developed yet. The harmonization of these opposite requirements is difficult and sometimes involve conflicts and must be based on compromises. IAEA exists to develop solutions and systems that satisfy the requirements of both the nuclear and pharmaceutical authorities.

For handling of radioactive products that are not used as pharmaceuticals (so — called radiochemicals) and for sealed radioactive sources, only radiation protection and radioactive contamination protection are necessary.

The main requirements for equipment and tools in hot cells that are used for the execution of manufacturing operations (e. g., rotating knives for cutting targets, dis­tillation equipment, pipettes for dispensing, magnetic stirrers, heating devices, auto­claves, ampoule capping devices) are operability with manipulators and small size. Such equipment and tools have become more and more automated. Automation fosters not only modernization but also radiation protection for humans and quality assurance. Modern isotope manufacturing technologies are already automated and computer controlled, in which the need for human interaction is minimal.

An important environmental aspect is the safe deposition of radioactive material generated as radioactive wastes in the manufacturing process. The usual approach for short-lived radionuclides is storage until decay, while for long-lived ones is depo­sition. This implies that liquid radioactive wastes are first bound to cement, placed into metal drums, and then, together with other solid radioactive wastes, are trans­ported to authorized radioactive repositories (see Section 7.3) for final disposal.

Further Reading

Bouissieres, G., Chastel, R. and Vigneron, L. (1947). Etats de dispersion du polonium dans l’eau, l’alcool et l’acetone. Comptes Rendus 224:43 —45.

Choppin, G. R. and Rydberg, J. (1980). Nuclear Chemistry, Theory and Applications. Pergamon Press, Oxford.

Elvidge, J. A. and Jones, J. R. (1979). Isotopes: Essential Chemistry and Applications. The Chemical Society, Burlington House, London.

Erbacher, O. (1942). Radium und isotope. In: Handbuch der Analitischer Chemie (eds.

Fresenius, R., Lander, G.). Springer, Berlin, p. 403.

Firouzbakht, M. L., Schlyer, D. J. and Fowler, J. S. (2006). Cryogenic target design considera­tions for the production of [F]fluoride from enriched [O]carbon dioxide. Nucl. Med. Biol. 26:749—753.

Friedlander, G., Kennedy, J. W., Macias, E. S. and Miller, J. M. (1981). Nuclear and Radiochemistry. Wiley, New York, NY.

Hahn, O. 1926a. GesetzmaBigkeiten bei der Fallung und Adsorption kleiner Substanzmengen und ihre Beziehung zur radioaktiven Fallungsregel. (Nach gemeinsam mit Hrn. O. Erbacher und Frl. N. Feichtinger ausgefiihrten Versuchen) Ber. Dtsch. chem. Ges. 59:2014—2025. Published Online: Jan 23 2006. DOI:10.1002/cber.19260590855.

Hahn, O. 1926b. “http://www. springerlink. com/content/x15543368334611k/7p52db46d7d6a 6f40e0979c7bbf98ef60f9&pi59” fiber die neuen Fallungs — und Adsorptionssatze und einige ihrer Ergebnisse. Naturw. 14:1196—1199.

Hahn, O. and Imre, L. (1929). fiber die Fallung und Adsorption kleiner Substanzmengen. III. Der Adsorptionssatz, Anwendungen, Ergebnisse und Folgerungen. Z. physikal. Ch. (A) 144:161 — 186.

Haissinsky, M. (1964). Nuclear Chemistry and its Applications. Addison-Wesley, Reading, MA.

IAEA TECDOC-1341 (2003) and IAEA Technical Reports Series No.63 (1966)

IAEA Safety Series No.1 (1973). Safe Handling of Radionuclides. International Atomic Energy Agency.

IAEA Technical Reports Series No.63 (1966). Manual for Radioisotope Production. International Atomic Energy Agency.

IAEA-TECDOC-1065 (1999). Production technologies for molybdenum-99 and technetium — 99m, International Atomic Energy Agency.

IAEA-TECDOC-1340 (2003). Manual for reactor produced radioisotopes, International Atomic Energy Agency.

Lambrecht, R. M. and Morcos, N. (1982). Application of Nuclear and Radiochemistry. Pergamon Press, New York, NY.

Lieser, K. H. (1997). Nuclear and Radiochemistry. Wiley-VCH, Berlin.

McKay, H. A.C. (1971). Principles of Radiochemistry. Butterworths, London.

Murray III, A. and Williams, D. L. (1958). Organic Syntheses with Isotopes. Interscience Publishers, New York, NY.

Wahl, C. A. and Bonner, N. A. (1951). Radioactivity applied to Chemistry. John Wiley and Sons, Inc., New York.

As discussed in Section 5.5.3, the interactions of a neutron with matter are defined by its neutrality, the magnetic momentum, and the de Broglie wavelength (about 1010m). The most characteristic interactions are the nuclear reactions and the scattering phenomena. The analytical methods involving neutrons utilize the following characteristics of neutrons:

• Having no charge, neutrons can be captured easily by the different atomic nuclei. Except for helium, all atoms can capture neutrons, a fact that makes them ideal for analytical purposes.

• Neutrons interact with the nuclei, and light and heavy elements can be analyzed at the same time.

• Neutrons have magnetic moments. The scattering methods based on the interaction of the neutrons with the nuclei and the magnetic field of matter provide information on both the nuclei and the magnetic field.

• The information obtained is on a molecular scale because of the very short de Broglie wavelength of neutrons.

• The energy of the neutrons can vary widely and can be compared to the energy of atomic and molecular motions.

• The range of neutrons is fairly large; thus, microscopic properties of bulk phases can be studied, even in industrial sizes.

• Neutrons are indestructible: biological, archeological, criminal, and other kinds of sam­ples can be analyzed without destruction.

The application of neutrons in the natural sciences was discussed in Section 5.5.3. The different types of NAA and neutron scattering will be discussed

next.

There are three main fields of nuclear medicine.

12.1.1 In Vitro Diagnostics

The meaning of in vitro is “measurement in a vial.” In this case, the patient does not make direct contact with the radioactive material, but the sample (blood, urine, etc.) is taken and analyzed using a radioactive component; in most cases, the concentration of a constituent will be measured. The first such procedures were developed by Yalow and Berson (1959) to measure insulin and by Ekins (1960) to measure thyroxin concentrations in blood. Rosalyn Yallow was awarded the Nobel Prize for medicine in 1977 for developing several peptide hormone RIAs. For further details, see Section 12.3.

Natural radioactive isotopes have been present since the formation of the Earth and are produced continuously by nuclear reactions of cosmic rays with atoms in the atmosphere.

As seen in Section 6.2.5, the elements in the universe are produced by nuclear reactions. Of course, these nuclear reactions produce both stable and radioactive isotopes. The half-lives of some radioactive isotopes are several billion years, com­parable to the age of the Earth and the universe. These radioactive isotopes cannot be formed under natural conditions characteristic to the Earth; thus, as a result of the radioactive decay, their quantity and radioactivity have been decreasing contin­uously since the Earth was formed. However, because of these long half-lives, their radioactivity have been significant until now. These radioactive isotopes are called “nucleogenesis” or “primordial” isotopes and can be classified into two groups. The first group contains of the isotopes in the natural radioactive decay series (235U, 238U, and 232Th; see Figures 4.4—4.6). The most important members of these decay series are the parent nuclides (235U, 238U, and 232Th) and the daughter nuclides with relatively long half-lives and the daughter elements of these daughter nuclides, for example, 226Ra, 210Pb, 210Bi, and 210Po. Gaseous radon isotopes (222Rn, 220Rn) are especially important because they enter the lungs through breath­ing, and their solid daughter elements (the lead, bismuth, and polonium isotopes produced from the radon isotopes in the 238U and 232Th series) are incorporated in the lung tissues, causing internal irradiation. Many of these isotopes emit alpha par­ticles with a short range. The alpha particles transfer their high-energy radiation within a short range inside the lungs. Since the radioactive isotopes of the decay series are always present in the building material, radon gas accumulates in closed

Nuclear and Radiochemistry. DOI: http://dx. doi. org/10.1016/B978-0-12-391430-9.00013-5

© 2012 Elsevier Inc. All rights reserved.

spaces (such as houses and caves). Therefore, the activity of radon is an important part of the background irradiation affecting living organisms.

In the second group of the primordial isotopes, there are the long-life nuclei pro­duced during nucleogenesis, which transform into stable daughter nuclides in one step. For example, 40K, 50V, 87Rb, 113Cd, 115In, 123Te, 138La, 144Nd, 147,148Sm, 152Gd, 156Dy, 174Hf, 176Lu, 186Os, 187Re, and 190Pt isotopes can be mentioned in this context. The most important radionuclide in this group is the radioactive iso­tope of potassium, 40K. The potassium ion is an essential ion in living organisms; its quantity is significant and plays an important biological role. Of course, the abundance of 40K in living organisms is the same as in every other potassium com­pound. This means that the radioactivity of 40K that is present in the body of adult people is about 3500—4000 Bq, depending on the mass of the body. The 40K iso­tope emits gamma radiation with high energy (1.46 MeV) and the range of these gamma photons is long. Thus, gamma photons leave the human body, and so the living organisms irradiate each other.

Many natural radioactive isotopes are produced continuously via nuclear reac­tions of the nuclei of atmosphere (nitrogen, oxygen, and argon) with cosmic radia­tion. As seen in Section 4.3.6, the basic isotope of the radiocarbon dating, 14C, is produced from the 14N in the air in an (n, p) nuclear reaction (see Section 6.2.1). Beside radiocarbon, many radioactive isotopes are produced in this way, e. g., 3H, 7,10Be, 22Na, 26Al, 32,33P, 35S, 36Cl, and 39Ar. These nuclides form from the 40Ar isotope of air under the effect of the cosmic radiation by spallation (see Section 5.5.2).