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.

Figure 8.15 A clean room for aseptic handling of pharmaceuticals.

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.