Radiochemical and Radionuclidic Purity

The analyses most pertinent to each compound are determined by its intended use and the method of its synthesis. The specifications or acceptable numerical limits will depend upon the intended use and the requirements of applicable local procedures, institutional standards or government regulations. The level of detail with which analytical procedures are prescribed, the skill and care with which they are conducted and the quality of data interpretation all vary significantly, according to the expertise of the analyst and local standards of practice. Such differences can be expected to result in correspondingly higher or lower risk to the success of the studies in which the compounds are used. The goal for all analytical measurements should be to minimize subjectivity. 

Analyses pertaining to chemical identity are intended to provide evidence that the structure and, if appropriate, stereochemistry, of a compound are in accordance with that claimed. 

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Studies of short-lived radionuclide generators (4-6) do not adequately treat the quantitative problems of the daughter nuclide elution or those specific to their optimal clinical use. Two essential physical characteristics of a generator are the yield of the daughter nuclide and its radiochemical and radionuclidic purity. To realize the full potential of a short-lived radionuclide generator for medical studies requires that these two characteristics are optimized and are compatible with parameters important to clinical use such as total perfused volume and duration of the scintigraphic examination. 

Hammermaier A, Reich E, Bogl W (1986) Chemical, radiochemical, and radionuclidic purity of el-uates from different commercial fission Mo/ Tc generators. Eur J Nucl Med 12 41-46 Lin MS, McGregor RD, Yano Y (1971) Ionic aluminium (III) in generator eluate as an erythrocyte-agglutinating agent. J Nucl Med 12 297-299... 

RADIOPHARMACEUTICALS A radiopharmaceutical is a preparation of adequately constant composition, radiochemical and radionuclidic purity and uniformity of physiological (pharmacological) action for use in medicine as a diagnostic aid or therapeutic agent... 

Physicochemical Tests Physicochemical tests include the tests for the physical and chemical parameters of a PET radiopharmaceutical, namely physical appearance, isotonicity, pH, radionuclidic purity, chemical purity, and radiochemical purity. 

Isotopic composition can be expressed as either absolute or relative measurement, depending on the particular application. When isotopically labeled materials are used as tracers absolute values are determined. The isotopic (or radiochemical) purity is the percentage of label present in the specified chemical form that may include the position of the label or the enantiomorphic form of the compound. In contrast, radionuclidic purity is the percentage of the total radioactivity present as the specified radionu-lide and implies nothing about the chemical form of the radionuclides present. 

The radionuclidic and chemical purity of all the four organic positron emitters produced is generally >99%. Reference has been made above to radiochemical purity and specific activity, but they are more relevant to the subsequently labeled product rather than to the radionuclide itself. Thus the production technology of the commonly used PET radionuclides is well established. 

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. 

A generator should ideally be simple to build, the parent radionuclide should have a relatively long half-life, and the daughter radionuclide should be obtained by a simple elution process with high yield and chemical and radiochemical purity. The generator must be properly shielded to allow its transport and manipulation. 

The quality control tests fall in two categories biological tests and physiochemi-cal tests. The biological tests establish the sterility and apyrogenicity, while the physiochemical tests include radionuclidic, chemical, and radiochemical purity tests along with determination of pH, osmotic pressure, and physical state of the sample (for colloids). 

The suitability of a radionuclide for a particular medical application will depend upon its availability in a radiochemically pure form, its nuclear properties and its chemical properties. In respect of the first of these considerations it is necessary to eliminate any extraneous radiation sources from a material destined for medical use. This need for very high radiochemical purity has a bearing on the means by which the radionuclide is produced. One potential method is by nuclear fission of a heavy element. This approach has the advant e that carrier free radioisotopes of high specific activity may be produced. However, because the process produces a complex mixture of FPs, painstaking separation and purification of the desired radionuclide will be necessary. The problem is simplified somewhat by using a pure target isotope to produce an FP which has rather unique properties. Thus fission produces which may be separated from the other FPs by virtue of its volatility. Fission in pure may also be used to prepare Mo in carrier free form, although contamination by Ru, I and Te was a problem in early... 

Identity and purity, stability, and sterility and apyrogenicity. The identity and purity of radiopharmaceuticals is verified by determining the radionuclidic and radiochemical purity. Stability concerns the radioactive label, which is related to radiochemical purity at a certain time after preparation. Since Tc pharmaceuticals are formulated as sterile, pyrogen-free solutions, the safety requirements of drugs for parenteral use do apply. Safe handling of the radionuclide is equally important and must comply with Euratom Directives, regulated by national law for radiation protection, which also concerns the application of radionuclides in adults and in children for diagnostic procedures. 

QC on Ready-for-Use Products from a Manufacturer. These radiopharmaceuticals are to be administrated to the patient without further preparation. As the manufacturing is inspected by competent authorities in order to ensure a high quality of the production process, the QC in the hospital in most cases can be reduced to control of transport documents, labels, and radioactivity. Tests on radionuclidic or radiochemical purity are normally not required. 

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. 

An inqx)rtant consideration in the use of radionuclides is their radiochemical purity since, should several radionuclides of different elements be present in a tracer sample used in an experiment, the result could be ambiguous and misleading. In a radio-chemically pure sample, all radioactivity comes from a single radioactive element. If the radioactivity comes from a single isotope, the sample may be said to be radio-isotopically pure. 

Radionuclides that are used as comparison sources, e.g., for determining instrument count rate stability and as tracers, must be of sufficient radiochemical purity and activity to eliminate interference in counting and permit correction for decay, but in most instances they need not have an accurately known disintegration rate. The absolute count rate also is unimportant for energy calibration because only the energy must be accurately known. 

Activation analysis is the other field of radiochemical analysis that has become of major importance, particularly neutron activation analysis. In this method nuclear transformations are carried out by irradiation with neutrons. The nature and the intensity of the radiation emitted by the radionuclides formed are characteristic, respectively, of the nature and concentrations of the atoms irradiated. Activation analysis is one of the most sensitive methods, an important tool for the analysis of high-purity materials, and lends itself to automation. The technique was devised by Hevesy, who with Levi in 1936 determined dysprosium in yttrium by measuring the radiation of dysprosium after irradiation with neutrons from a Po-Be neutron source. At the time the nature of the radiation was characterized by half-life, and the only available neutron sources were Po-Be and Ra-Be, which were of low efficiency. Hevesy s paper was not followed up for many years. The importance of activation analysis increased dramatically after the emergence of accelerators and reactors in which almost all elements could be activated. Hevesy received the 1943 Nobel prize in chemistry for work on the use of isotopes as tracers in the study of chemical processes . 

Radionuclide and radiochemical purity are essential. The labeled substance must react identically to the analyte. 

Fifteen trace elements were determined at ng/g mass fraction levels in high purity Sn by Kolotov et al. (1996) using extraction chromatography on Teflon-supported tributylphosphate (TBP). Tin, together with Sb and In radionuclides, which are formed in secondary nuclear reactions of Sn during irradiation, were retained from 6 M HCl on the column. The Na was removed from the eluted trace element fraction by sorption on hydrated antimony pentoxide (HAP). Gas phase impurities of N, C, and O were also analyzed in the same material by radiochemical photon activation analysis via N, C, and detection. 

Solvent extraction and ion exchange are widely used to produce various radionuclides from irradiated targets. The common routine is that the target is dissolved in an aqueous phase, often a mineral acid, and then treated with a suitable extractant or ion exchanger to isolate the nuclide of interest. Several steps are often applied to obtain the desired radiochemical purity. 

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