Production of PET Radionuclides

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

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. 

Abstract Cyclotron products are gaining in significance in diagnostic investigations via PET and SPECT, as well as in some therapeutic studies. The scientific and technological background of radionuclide production using a cyclotron is briefly discussed. Production methods of the commonly used positron and photon emitters are described and developments in the production of some new positron emitters and therapeutic radionuclides outlined. Some perspectives of cyclotron production of medical radionuclides are considered. 

Nuclear Synthesis Except for radionuclides with ultrashort half-lives, like most PET radionuclides, the production of these is normally performed well in advance (see Section 1.3.4.1). Thus, the radionuclide is considered as a starting material and must undergo controls as a starting material. 

For PET radiopharmaceuticals we must always consider that synthesis processes must be extremely fast. Consequently, synthesis schemes with as few steps as possible must be used, and each of the steps must proceed with high efficiency. The incorporation of the radionuclide to the molecule should ideally be done in the final steps of the synthesis. In this way two objectives can be achieved reduce the overall synthesis time (thus increasing the yield) and reduce the number of side reactions and secondary undesired products obtained during the synthesis. 

The position of the radionuclide in the molecule of interest is also critical as it will affect the biological behavior of the radiopharmaceutical. Chemical reactions must be designed to be stereospecific in many cases, as the production of a mixture of different stereoisomers complicates the purification of the final radiopharmaceutical. Synthesis procedures must also be easy to automate, as very elevated activities are used for the synthesis of PET radiopharmaceuticals (several curies usually) and appropriate radiation protection systems must be used. 

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. 

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. 

More than 3,000 nuclides are known, of which approximately 270 are stable and the remainder are radioactive. The majority of radionuclides are artificially produced in the cyclotron and reactor. In PET technology, only positron-emitting radionuclides are required, and only a few positron emitters of all radionuclides have been suitably utilized in the clinical studies. These radionuclides include 11C, 13N, 18F, 150, etc., and are produced in the cyclotron. The operation of a cyclotron and the production of useful positron emitters are described below. 

Liquid targets are used in the production of many PET radionuclides, particularly 18F and 13N. Fluorine-18 is produced by using a liquid target of lsO-enriched water and so is 13N by using 5 nM ethanol in water. The target volume is small in the range of 3-15 ml under high pressure. Since lsO-water is expensive, it is customary to recover it for subsequent irradiation and the method of recovery is described in the later section. 

Since only a limited number of short-lived radionuclides are useful for PET imaging, production of those in routine clinical use and a few with potential for future clinical use are described here. A few essential long-lived positron emitters are also included. The different characteristics of these radionuclides are summarized in Table 7.2. 

Regarding the 0(p,n) F reaction, only one group had reported the activation cross sections (Ruth and Wolf 1979). A recent detailed study (Hess et al. 2001) established the data base firmly for this production route of the most commonly used PET radionuclide F. The results are shown in O Fig. 39.5. The yield can now be calculated up to 30 MeV. The resonances at 5.1,6.1 and 7.2 MeV are in agreement with those found in spectral measurements of emitted neutrons. 

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. 

The generator produced positron emitters find application mostly in PET studies at centers without a cyclotron. A discussion of generator preparation is beyond the scope of this article (for a detailed discussion, c O Chap. 40 in this Volume). Here a very brief account is given of the production of the two long-lived parent radionuclides concerned (cf. Qaim 1987 Qaim et al. 1993). 

His research on the production and potential medical application of radionuclides continued at the Institute of Nuclear Chemistry, Research Centre Jiilich GmbH, Germany, from 1991-1996. In 1996 he was appointed a University Professor for Nuclear Chemistry at the Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Germany. His current research activities are focused on the development and evaluation of PET radiopharmaceuticals, including radionuclide generator-based radionuclides. 

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