Selective Production of Exotic Species


Contact person: Dr. Fabiana Gramegna (INFN LNL) – ad interim

Area: Nuclear Physics, Health and Life Sciences, Applications with neutrons

SPES is a project related to the construction of a research infrastructure dedicated to the production of exotic beams for nuclear physics and astrophysics and for applications, especially in the medical field (radioisotope production).

The project is divided into four phases:

SPES alpha

SPES is a project related to the construction of a research infrastructure (Figure 1) dedicated to the production of exotic beams for nuclear physics and astrophysics and for applications, especially in the medical field (radioisotope production).


Figure 1: Plan of the SPES building at LNL.

The project is divided into four phases:


SPES alpha

The alpha phase relates to the installation and commissioning of a cyclotron B70. The SPES cyclotron can accelerate proton beam in an energy range between 35 and 70 MeV at high intensity (expected currents up to 750 mA). It (Figure 2) weighs 190 tons, has a diameter of 4.5 m and a height of 2.0 m, is equipped with four sectors, a resistive magnet for a maximum magnetic field of 1.6 T and has two extraction points for the beam to allow simultaneous activity on two experimental points, one dedicated to nuclear physics, the other related to applications. The SPES building houses the cyclotron, the irradiation areas or bunker dedicated both to the production of exotic beams (ISOL) and to the production and research of radioisotopes (LARAMED, ISOLPHARM), some laboratories for the study, characterization and radiochemistry for production of radiopharmaceuticals, other laboratories for the production and characterization of UCx targets, an activity area for experimentation with exotic non-re-accelerated beams, the cyclotron control area, the area dedicated to the imposing plant at the service of the accelerator and target systems and bunker ventilation, which must be operated in slight depression.


Figure 2: Cyclotron and some beam lines.

SPES beta

The beta phase of the SPES project involves the installation of an infrastructure for research in nuclear physics with the availability of exotic beams coming from ISOL-type production systems, due to the interaction of an intense beam of protons (200 μA) with different targets capable of sustain up to about 10 KW of power. Among the different targets, the one of greatest interest is Uranium Carbide UCx, through which 1013 fissions / s can be reached, to allow the production of different exotic elements that can be extracted from the source with good intensity (for example 132Sn to 109 p / s). The nuclear species formed in these processes are characterized by an excess of neutrons, “exotic” systems not present on earth due to their short life.

The exotic beams produced can be directly sent to the experimental targets (low energy experimentation) or they can be re-accelerated by the ALPI post-accelerator (Linear Accelerator for Heavy Ion) of the LNL (for example, 132Sn up to 10 MeV / nucleon). The accelerated particle beam interacts with suitable targets, chosen to produce new nuclei extremely rich in neutrons, such as those generated in advanced stellar phases. The nuclear reactions produced allow us to study different characteristics of nuclear matter far from the valley of stability and of the nuclei that have characterized the evolution of the universe. In this way it will be possible to study in the laboratory what happens in the heart of the stars, obtaining crucial information for the knowledge of our universe.

The evolution of the stars and their end of life depend critically on the play between the gravitational force, which tends to make them collapse, and the nuclear reactions in their nucleus that release energy and generate expansion. Initially the stars burn hydrogen transforming it into helium, then helium into carbon, and so on to generate by fusion increasingly heavier chemical elements, up to iron.

Even heavier elements, between the stability valley and the drip line, are formed in the final and explosive phases of type II supernovae by absorption of neutron fluxes, through the so-called r process (r=rapid). The other heavy elements, for the most part included in the stability valley, are produced during the life of the star with neutron fluxes of several orders of magnitude smaller than in the previous case, by means of a process called s (s=slow).

Several experimental apparatuses have been developed for the study of reactions with low-energy exotic ions such as the ribbon station for beta decay studies and with re-accelerated beams such as the AGATA and GALILEO gamma spectrometers, the PRISMA magnetic spectrometer, the multi-detector for particles GARFIELD (Figure 3).


Figure 3: Drawing of the AGATA configuration in hall I. GALILEO experimental setup in hall II. PRISMA experimental apparatus in hall I, to be coupled to AGATA. GARFIELD experimental setup in hall III.

For the study of reactions and nuclear structure with radioactive beams in which the more exotic species can be expected to be produced with very low intensities, of the order of 102-103 pps, an active target detector (ATS) has been developed. It is a tracker that functions as a Time Projection Chamber (TPC) in which the gas used for the detection is, at the same time, the target for the nuclear reaction of interest. This brings great advantages in terms of brightness and allows to study even the most exotic species through elastic and inelastic diffusion reactions with very little intense beams.

SPES gamma

Radiopharmaceuticals (Figure 4) are a fundamental tool of modern nuclear medicine, to diagnose and treat numerous diseases, exploiting the metabolic processes that occur at the cellular level. They are composed of a biologically active part, which works as a selective key for the specific cellular process (known as a targeting agent), and a part that functions as a binder, to ensure the chemical stability of the compound within the body. Finally, from a radionuclide, chemically linked to a molecule, having the suitable characteristics, which emits radiation, that is the tool that interacts with biological tissues to obtain information (images) or to selectively damage them (therapy). Radionuclides are in fact radioactive atoms which, after a certain time, called half-life, decay by emitting radiation and are transformed into a different chemical element; each radionuclide is characterized by a half-life and a specific radiation, whose characteristics can be exploited in medicine (γ or β + radiation for diagnosis; α, e- Auger or β- radiation for therapy).


Figure 4: Production diagram of a radiopharmaceutical.

For this reason, it is important to have numerous radionuclides available, with different physical / chemical characteristics, in order to be able to build increasingly effective and selective radiopharmaceuticals. The production of radionuclides, both those already used in nuclear medicine and the innovative ones, are the fundamental objective of the phase gamma of the SPES project. To this end, the cyclotron and the skills developed within the LNL in nuclear physics, radiochemistry, materials science, engineering, etc. will be exploited. Research on radionuclides / radiopharmaceuticals is, in fact, a typical example of an emerging research scenario, in which a markedly interdisciplinary approach is required to successfully carry out challenging research programs.

Taking advantage of the peculiarities of the SPES facility, two possible production processes have been developed which refer to the LARAMED and ISOLPHARM projects (Figure 5).


Figure 5: The LARAMED and ISOLPHARM (SPES gamma) projects.

LARAMED project

LARAMED, (acronym for the Laboratory of RAdionuclides for MEDicine) is the research program that includes several targeted projects, all focused on the study and production, in an alternative / innovative way, of radionuclides of interest, both for diagnostics and for therapy (for example 99mTc, 64,67Cu, 47Sc, 51,52Mn, 89Zr, etc.) using the so-called “direct” activation method. This consists in irradiating, with the proton beam that will be available from the cyclotron, a target with the appropriate characteristics (material, thickness, support, etc.) for a time such as to maximize the production of the radionuclide of interest, while minimizing that of the contaminating radioisotopes. The optimization of production, or the identification of the ideal characteristics of the target and the physical parameters of the radiation, starts from the knowledge of the nuclear reactions involved. Skills in mechanical engineering and materials science are essential to try to increase the intensity of the proton beam as much as possible, without damaging the irradiated target, in order to increase the final activity of the radionuclide produced. At the end of the bombardment, the target is chemically treated to extract and purify the radionuclide of interest, separating it from all other chemical species produced. Once the purified product has been obtained, it is possible to carry out quality controls (to guarantee the chemical, radiochemical and radionuclide purity of the product, identified by appropriate protocols) and proceed with the subsequent phase of marking the radiopharmaceutical, i.e. by chemically binding the radionuclide to the chemical compound (existing or innovative) to obtain the desired radiopharmaceutical. Proposed a few years ago, the main objective of the LARAMED project is to focus research on new radionuclides that have a potential interest in nuclear medicine. Although not yet available (for both scientific and clinical applications) they may play a key role in improving approaches in patient treatment and clinical research. Furthermore, LARAMED will also focus on the search for alternative production routes (i.e. nuclear reactions based on production techniques using accelerators) also for those radionuclides produced in a conventional way, by means of nuclear reactors, and already used in nuclear medicine departments in hospitals (for example 99mTc, used for more than 50 years in hospitals all over the world).


Figure 6: Scheme of radio nuclide production and laboratory facilities.


Among the fundamental aspects in the development of new radiopharmaceuticals is the study of the best strategies to ensure the availability of radionuclides with a sufficiently high degree of purity to ensure the quality and effectiveness of the final compound. Therefore, in addition to the conventional production procedures, mostly based on the use of accelerators or reactors, INFN has patented an innovative method, ISOLPHARM, based on the exploitation of the ISOL technologies developed for the SPES project. According to this technique, the radioactive beam leaving the SPES facility, after having been mass purified by electromagnetic separators, is collected on specific substrates, called deposition targets. In this way, the radionuclide of interest is implanted in the substrate with any isobaric contaminants, however, characterized by a different atomic number Z (and therefore are different chemical elements). The deposition target is then dissolved and a chemical separation step (if necessary) allows the elimination of all contaminants, ensuring a solution containing only the radionuclide of interest, which can be used for subsequent radio pharmaceutical processes.

The ISOLPHARM method has numerous advantages: it is versatile as it would allow the production of a wide range of radionuclides, both for diagnostic and therapy applications; it is flexible because different radionuclides can be extracted from the same production target, it is sufficient only to change the settings of the mass separators to collect a different family of isobars, it is innovative because it will allow the production of innovative nuclei, difficult to obtain with traditional techniques (for example 111Ag), and has a lower environmental impact than nuclear reactors.



Figure 7: Scheme of the production of radionuclides with the ISOLPHARM method and a detail of the target developed at LNL.

SPES delta

The SPES cyclotron is also used to produce intense neutron beams. Neutrons are generated by reactions between the proton beam and targets of beryllium, lithium and tungsten. Neutrons are nuclear particles that have no electric charge and therefore interact only with the nuclei of atoms. The absence of electric charge makes them special, both because they are not easily manageable (they cannot be stopped or bent using electric or magnetic fields) and because they are very penetrating (they can even cross meters of material). Neutrons have an average life of about a quarter of an hour, so they are not present in the universe, except in certain regions. Neutrons are created for example by the interaction of cosmic rays with matter: on earth they are produced by collisions with the atmosphere. Neutrons are also very harmful to both health and electronic devices.

The SPES neutron beam facility (NEPIR) aims to study the effects of neutrons in many fields, from electronics to space missions, passing through fourth generation nuclear reactors and incinerators of radioactive waste without ever neglecting physics fundamental and the study of materials.

When a neutron hits an electronic device, the reaction that occurs leads to damage to the device, which can be temporary (SEE) or permanent (SEU). In any case, if the device is complex (database server or for telecommunications, satellites, airplanes or ships) the damage causes a fault of the device, with consequent temporary or permanent damage. The rush to miniaturize electronic devices has led to an exponential increase in the likelihood of neutron-induced damage. The development of electronics in every field of our life therefore requires electronic systems capable of withstanding neutron radiation, which, due to their peculiarity, are not easily shielded.

Today, our technology would allow us to take humans to Mars with relative ease. The space vehicles are capable of this and the time spent in space is sufficiently long (think of the stays on the space station). The problem is to get them to arrive and come back alive! The biggest problem is radiation and of these, the neutron ones are the most difficult to manage. It is necessary to invent shields, therefore materials, capable of being light, compact and having excellent shielding qualities. The NEPIR facility, in collaboration with ASI (SPARE project), is responsible for testing innovative materials for space missions and studying models suitable for predicting the effects of neutron radiation on materials and humans in view of a new colonization of space.

The effects of radiation on the living organism cause permanent and lethal damage; in addition to the study of materials capable of shielding or reducing these radiations, the effects of cell damage induced on hibernating beings are studied. Hibernation can be artificially induced and corresponds to a kind of lethargy. It has been found that in hibernating living beings, radiation-induced damage is considerably less than in the waking state, possibly due to an increased efficiency of the cellular repair system. The study of radiation on living systems, in addition to being a possibility for space missions, also has many other fields of application in cancer medicine.

Let's end with a mention of fourth generation nuclear reactors. The new reactors will be able to burn much more efficiently and produce far less waste than current reactors. A reactor works through an energy-producing fission reaction and a neutron capture reaction. The balance is very delicate: if enough neutrons are not absorbed, the reaction becomes uncontrolled (explosion, at least a nuclear bomb if the neutrons are not absorbed at all), if too many neutrons are absorbed the reaction goes off. It is therefore fundamental for the functioning of nuclear fission reactors (both today and, even more so, future ones) to study the reactions induced by neutrons, both capture and fission, passing through many other reaction channels and the energies of the new reactors. they can open.

The NEPIR facility will produce a neutron beam with a spectrum very similar to that of the neutrons present on earth (up to an energy of 70 MeV) and almost monochromatic beams in energy, continuously variable from 25 to 70 MeV. There will also be a direct line of protons for the study of the reactions induced by these particles.