Cyclotron radionuclides

S. L. Waters, D. J. Silvester, Inorganic Cyclotron Radionuclides, Radiochim. Acta 30,163 (1982)... 

The production of the various metallic radionuclides with utility to either diagnosis or treatment are described, separated by route of production (either cyclotron/accelerator or reactor). 

Cyclotrons and accelerators are sources of charged particles (i.e., protons, deuterons, a particles, etc.), and the radionuclides produced are generally proton rich and decay by positron emission and/or electron capture. A positive ion beam is eventually extracted from the cyclotron, regardless of whether positive or negative ions were accelerated. The isotope of interest is separated from the target for use in chemical syntheses. Accelerator- or cyclotron-produced radioisotopes tend to be the most expensive as only one radionuclide is produced at a time. 

The number of naturally occurring radionuclides is limited and few are of analytical value. For the majority of purposes artificial radionuclides are manufactured. Bombardment reactions are generally used in their production. A suitable target material is exposed to an intense flux of the appropriate particles in a nuclear reactor or particle accelerator such as a cyclotron. Thermal neutrons in the reactor... 

Ultra short lived radionuclides, with a half-life of a few seconds to a few minutes are readily available from long-lived parent radionuclides adsorbed to an organic or inorganic ion exchange support matrix (1-3). These radionuclide generator systems are an inexpensive alternative to an on-site cyclotron, especially for positron emitters used for positron emission tomography (PET). 

Production of Sr-82. An important consideration in the development of radioisotope generators is the availability, cost, and radionuclidic purity of the long-lived parent. In the case of Sr-82, the 25 day radionuclide is needed in 100-200 mCi amounts in order to provide adequate elution yields of Rb-82 from one loading of Sr-82 every three months. Initially the Sr-82 for the generator was produced at the Lawrence Berkeley Laboratory (LBL) 88-inch cyclotron by the Rb-85 (p,4n) Sr-82 nuclear reaction (12). However, because of the long irradiation time required to produce... 

Automated radionuclide generators capable of providing precise dose delivery of multi-millicurie amounts of short-lived positron emitters on demand from a safe and easily operated system are an attractive alternative to on-site cyclotrons for positron emission tomography. The availability of curie quantities of parent radionuclides from national laboratories and the development of microprocessor automation makes it feasible to utilize these generators in the clinical setting. 

The major isotopes used in PET are lsO (half-life = 20 min), 1JN (half-life = 10 min), nC (half-life = 20 min), and WF (half-life = 110 min). Half-life spans are approximate, The foregoing isotopes are produced by a nearby cyclotron, They are either administered promptly, or are rapidly incorporated into appropriate molecules, such as metabolic substrates, substrate analogues, or drugs, which are then administered. Minicyclotrons for generating radionuclides are becoming available as of the late 1980s. 

There are several hundred radionuclides that have been used as radiotracers. A partial list of the properties of these nuclides and their production methods are shown in Table 4.1. The three common production mechanisms for the primary radionuclides are (n,y) or (n,p) or (n,a) reactions in a nuclear reactor (R), charged-particle-induced reactions usually involving the use of a cyclotron (C), and fission product nuclei (F), typically obtained by chemical separation from irradiated uranium. The neutron-rich nuclei are generally made using reactors or... 

As indicated above, a combination of reactor and cyclotron irradiations is used to prepare most radionuclides. While many of these radionuclides are available commercially, some are not. In addition, nuclear structure, nuclear reactions, and heavy-element research require accelerator or reactor irradiations to produce short-lived nuclei or to study the dynamics of nuclear collisions, and so on. One of the frequent chores of radiochemists is the preparation of accelerator targets and samples for reactor irradiation. It is this chore that we address in this section. 

Many radionuclides can be produced in cyclotrons, thus avoiding the use of more costly nuclear reactors. Many research hospitals now have cyclotrons to provide shortlived radionuclides of carbon, nitrogen, oxygen, and fluorine. The longer-lived products are produced commercially or in government laboratories.25,26 28A list of major isotopes and their uses is shown in Table 21.9,... 

Lagunas-Solar, M., Cyclotron Production of No-Carrier-Added Medical Radionuclides, 7th Conference on the Applications of Acceleration in Research and Industry, Denton, TX, 1982. 

Particle Accelerators Cyclotrons Both linear and circular particle accelerators (cyclotrons) can be used, but the latter have many advantages and are mainly used for the production of clinically relevant radionuclides. 

An interesting concept that must always be taken into account in cyclotron-produced radionuclides is the saturation activity characteristic of each target and each nuclear reaction. The saturation activity is the activity of the radionuclide in which the secular equilibrium is obtained between the activity produced in the target and the disintegration of the radioisotope. The activity produced at a target can be calculated by the equation... 

Positron emission tomography has become a widely used diagnostic technique in nuclear medicine. Ultrashort half-live radionuclides are used in these cases, and such radionuclides are mostly obtained in small cyclotrons with high yields and short irradiation times. The overall process will be described further in this chapter when PET radiopharmaceuticals are described. 

The main advantage of the generators is that they can serve as top-of-the-bench sources of short-lived radionuclides in places located far from the site of a cyclotron or nuclear reactor facilities. 

PET Radiopharmaceuticals PET radiopharmaceuticals are labeled with shortlived positron-emitting radionuclides. Such radionuclides can either be produced in a cyclotron or obtained from an appropriate radionuclide generator. 

Production of the radionuclide in the cyclotron and sending it to the PET radiopharmaceutical laboratory... 

A PET radiopharmaceutical laboratory must include the cyclotron bunker (where positron-emitting radionuclides are produced), the production laboratory, the quality control laboratory, and several different ancillary areas. 

In modem machines, protons, deuterons and a particles with energies of several 100 MeV up to about 1 GeV are available. Proton linacs serve frequently as injectors of 50 to 200 MeV protons into proton synchrotrons. For the production of radionuclides, relatively small cyclotrons are used by which particle energies of the order of 10 to 30 MeV and ion currents of the order of 100 pA are available. Radionuclides obtained by reactions with protons exhibit decay or electron capture (s). 

Several positron emitters are of practical importance in nuclear medicine for positron emission tomography (PET). Some are listed in Table 12.6. Protons or deuterons with energies varying between about 10 and 40MeV are available in small cyclotrons ( baby cyclotrons ) and are applied for the production of suitable radionuclides. 

The spectrum of radionuclides available for application in the life sciences broadened appreciably with the invention of the cyclotron by Lawrence in 1930 and the possibility of producing radionuclides on a large scale in nuclear reactors in the late 1940s. By application of T and C, important biochemical processes, such as photosynthesis in plants, could be elucidated. 

The production of short-lived positron emitters has been described in section 12.2. By interaction with electrons, the positrons are annihilated and two y-ray photons of 511 keV each are emitted simultaneously in opposite directions. By measuring these photons by means of a suitable arrangement of detectors, exact localization of the radionuclides in the body is possible. This is the basis of positron emission tomography (PET), which has found broad application in nuclear medicine. The most frequently used positron emitters are listed in Table 19.2. They are preferably produced by small cyclotrons in the hospitals or nearby. 

Positron emitting nuclides have very short half lives, on the order of minutes to tw o hours. This makes operation of a cyclotron and a radiochemistry laboratory essential to the use of PET scanners. is the longest radionuclide with a half-life of 1.87h, making a central production facility within a city feasible for radiopharmaceuticals employing this nuclide. Most clinical PET facilities have on-site cyclotrons and radiopharmaceutical laboratories to allow the use of short-lived isotopes in clinical studies. 

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