Production of Radionuclides and Labelled Compounds

Nowadays, nuclear medicine has become an indispensible section of medical science, and the production of radionuclides and labelled compounds for application in nuclear medicine is an important branch of nuclear and radiochemistry. The development of radionuclide generators made short-lived radionuclides available at any time for medical application. New imaging devices, such as single photon emission tomography (SPET) and positron emission tomography (PET) made it possible to study local biochemical reactions and their kinetics in the living human body. 

Research in nuclear and radiochemistry comprises Study of radioactive matter in nature, investigation of radioactive transmutations and of nuclear reactions by chemical methods, hot atom chemistry (chemical effects of nuclear reactions) and influence of chemical bonding on nuclear properties, production of radionuclides and labelled compounds, and the chemistry of radioelements - which represent more than a quarter of all chemical elements. 

In the reactions leading to the desired product (column A) many factors must be considered. They are of such importance that we devote several separate chapters to this Ch. 12 on nuclear reactions, Ch. 13 on particle accelerators and Ch. 15 on production of radionuclides. The incorporation of the radionuclide in a chemical compound (labelling, 15.5.3) provides it with unique properties, such as specific biological affinity ( 9.5.1). When such labelled compoimds are taken up by organisms (A4b - Bl) they move to specific sites in the organs, signalling normal or abnormal behavior. When used in medicine (primarily Cl and C3) these compounds are referred to as radiopharmaceuticals (A4b). 

The application of radionuclides to physiological studies of wild organisms can be classified into either of two categories based on the reason for the use of the radionuclide (1) interest is not in the radionuclide per se, but only as it serves the purpose of identifying a labeled compound, e.g., tritiated water and (2) interest is in the specific radionuclide or its stable form, e.g., the study of the biological half-life of the fission product Cs. 

Decay products of the principal radionuclides used in tracer technology (see Table 1) are not themselves radioactive. Therefore, the primary decomposition events of isotopes in molecules labeled with only one radionuclide / molecule result in unlabeled impurities at a rate proportional to the half-life of the isotope. Eor and H, impurities arising from the decay process are in relatively small amounts. Eor the shorter half-life isotopes the relative amounts of these impurities caused by primary decomposition are larger, but usually not problematic because they are not radioactive and do not interfere with the application of the tracer compounds. Eor multilabeled tritiated compounds the rate of accumulation of labeled impurities owing to tritium decay can be significant. This increases with the number of radioactive atoms per molecule. 

In certain experiments, the primary radionuclides may be used directly, but usually the investigator wants to secure a specific labeled compound for use in radio-tracer experiments. Before considering the details of the production of these labeled compounds, let us discuss the nomenclature and rules used in referring to them. 

In many situations, the experimenter will prefer to buy labeled compounds from commercial suppliers rather than attempt to synthesize them. The radiochemical purity of such purchased compounds cannot be assumed. Radiation-induced selfdecomposition (radiolysis) can result in the formation of a variety of labeled degradation products, which must be removed before experimental use of the compounds. The extent of radiolysis depends on the nature of the labeled compound, how long it has been stored, and the manner of storage. Radiolysis is most significant with low-energy (3 emitters (especially tritium) since the decay energy is dissipated almost entirely with the compound itself. Furthermore, impurities involving other radionuclides may be present. 

Most countries have one or more suppliers of radiochemicals. To locate suppliers, the simplest way is often to contact the nearest nuclear c ter, as it may be a producer of radionuclides, the national radiation safety organization, or the annual Byers Guide of common nuclear journals. Product catalogs list the type of radioactive sources and compounds available, purity of the products, maximum and specific activities, radiation decay characteristics, accuracy of standards, labeling position, etc. 

Abstract Methods for the synthesis of compounds labeled with the short-lived positron emitting radionuclide are described. Important aspects on how to achieve high specific radioactivity and the need for technical solutions to establish a reproducible routine tracer production are pointed out. Examples of positron emission tomography (PET) as a tool in drug development are also included. 

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