Production of Cyclotron

Positron emission tomography in conjunction with radiopharmaceuticals labeled with positron emitting radionuclides opens the possibility of visualizing in vivo in an atraumatic way fundamental parameters of metabolism in man. The main positron emitting radioisotopes carbon-II, oxygen-IS, nitrogen-13 and fluorine-IR used for labeling radiopharmaceuticals (sugars, aminoacids, fatty acids and drugs) are produced by nuclear reaction involving charged particles accelerated with cyclotrons. Small cyclotrons producing R l-'eV deuterons and 15 l~eV protons seem optimal for the routine production of these radionuclides. Some specific medical examples are given illustrating the potency of this new tool. Gamma emitting radioisotopes were proved very early to give unique biochemical or physiological information when injected in a living organism in a suitable chemical form. The possibility of external detection offers a non invasive way to follow changes in the distribution of the tagged species. Using adequate detectors, regional distribution as well as quantitative kinetic parameters may be obtained in such a way that abnormalitiesof metabolism may be observed with great accuracy. However the radioisotopes used for this purpose must fulfil a number of physical and chemical criteria. According to the size, and density of the human bod~ the turnover and sensitivity to radiation damage of living biological matter, the disintegration scheme and the half-life of the useful radioisotopes should be 1'.ept within narrow limits. For most applications the half-lives of the radionuclides used to date fall between a few seconds and a few days. Beta/gamma or pure gamma emittors with gamma ray energT ranging from a few tenths to a few hundred keV are the most commonly used with an ideal energy around 150 to 200 keV to insure a minimum loss of information from absorption in the biological matter and a maximum sensitivity of the detection devices. Alpha emitting radioisotopes are avoided because of the high ionization of these particles which would deliver a radiation damage to the target organ incompatible with a diagnostic test. According to the chemical criteria a good radionuclide has to be an isotope of the component elements entering in the composition of biological matter in order to reliably trace a biological or physiological event. Hith few exceptions (radioiodine in endocrinology, radio-iron or cobalt in hematology) the radioisotopes used so far do not entirel'"meet these criteria. Technecium 99 m which is used for more than 80 % of the diagnostic tests in Nuclear Eedicine has ideal physical characteristics but is not a good biochemical tracer since its presence can modify the chemical struc-· ture and thus the metabolism of a labeled organic substrate. In the last ten years there have been a considerable effort to make new radionuclides available to better respond to the needs of modern Nuclear Medicine. Positron emitting radioisotopes are ideal in this respect since their mode of disintegration allows them to be detected quantitatively and located with accuracy by tomographic devices. In addition, those which are of interest for following biological phenomena such as carbon 11, nitrogen 13, oxygen 15, fluorine 18 and a few others, are short lived radionuclides and thus can be injected to humans without giving rise to high radiation doses. However, it must be kept in mind that some drawbacks are the consequence of these short half-lives. Some are methodological : the need of having at the same site the means of producing and incorporating them in radiopharmaceuticals and of in vivo measurement for achieving the medical studies, others are directly concerned with the type of physiopathological parameters which will be obtainable. Only short term studies will be possible eliminating the possibility of observing slow metabolic pathways. l~ny reviews have already been published on this subject (1,2) and the scope of this paper will be focussed on a few specific points in relation to the production of the short-lived positron emitting radioisotopes, their incorporation in radiopharmaceuticals and some medical applications under development in a few medical centers. I) Production of short lived positron emitting radioisotopes and radiopharmaceuticals. The short half-life of the radioisotopes under consideration necessitates that the means to make and to use them be available at the same site. This means that the accelerator for isotope production, usually a cyclotron, the chemistry laboratory for radiopharmaceutical synthesis, and the detection device with other facilities for the medical study should all be located in or adjacent to the hospital. Proceedings of the 9th International Conference on Cyclotrons and their Applications September 1981, Caen, France