Founded in 1951, the Italian Institute for Nuclear Physics (INFN) is the public research institute that has taken up the scientific legacy of Enrico Fermi and, for more than seventy years, it conducted cutting-edge research in the field of nuclear, particle, and astroparticle physics, as well as in developing technologies for research and their applications to benefit society. Among the four INFN National Laboratories, the Legnaro National Laboratories (LNL, Legnaro, Padova) are internationally recognised to conduct state-of-the-art research in the field of nuclear physics and its applications, thanks to the five particle accelerators and related technologies there available.
The LNL’s future is the SPES (Selective Production of Exotic Species) project, that aims at providing a unique facility for both basic research in nuclear science and applied research in radioisotopes production for medicine. The heart of SPES is a high power cyclotron accelerating protons up to 70 MeV with very high intensities that can reach 700 µA. On the European landscape SPES will be the only facility that can contribute to innovative radionuclide production by using two complementary methods: the direct activation method using the LARAMED facility and the ISOL technique using the ISOLPHARM facility. The direct activation method consists of the proton irradiation of a dedicated target, whose manufacture is specifically optimized to produce the medical radionuclide of interest (i.e., material, isotopically enrichment, purity, thickness, etc.), that after the bombardment has to undergo a radiochemical process in order to extract and purify the medically relevant radioisotope from all the irradiated material, including the co-produced contaminants. On the other hand, in the ISOL technique the proton beam impinges on a thick Uranium Carbide (UCx) target generating a characteristic set of fission-fragments, most of which are released from the latter thanks to the high operational temperature levels, generally above 2000°C. The released nuclei migrate towards an ion source where neutral atoms are transformed into singly charged positive ions that can be extracted into a particle beam thanks to intense electric fields. The extracted radioactive ion beam is further transported, focalized and injected into a Wien filter, an electromagnetic velocity separator that is used as mass spectrometer. Such device is employed to deflect and dump the beam particles characterized by a different mass respect to the ions of interest. The output of the Wien filter is an ideally isobaric ion beam, composed by the radionuclide of interest together with possible contaminants of other chemical elements with the same mass, that can be collected onto appropriate deposition substrates. The complementarity of the methods guarantees, at SPES, a large versatility in the production of the emerging radionuclides under the spotlight of the scientific community whose supply is yet limiting their preclinical and clinical use. The key role of new medical radionuclides for innovative radiopharmaceutical is the possibility to adapt the emitted radiation for early diagnosis (i.e., using γ or β⁺ emitters) or tailored therapy (i.e., using α, Auger and conversion e^– or β^– emitters). Lately, with the “theranostic” approach, i.e. the use of a single radionuclide or pairs that can be labelled to the same radiopharmaceutical, it is possible to perform both therapeutic and diagnostic procedures. The main advantage of theranostic radiopharmaceuticals is the possibility to select the patients with a high chance to positively respond to the specific treatment, avoiding the administration of useless (and expensive) drugs. In fact, it is possible first to use a diagnostic radionuclide to obtain a SPECT (Single Photon Emission Computed Tomography) or PET (Positron Emitted Tomography) image to verify the correct uptake of the tissue of interest, followed by the administration of the right therapeutic amount using the same radiopharmaceutical labelled with a radionuclide whose radiation is useful for the treatment.
The medical community is thus fostering the production of emerging radionuclides (both for diagnosis and therapy), to meet the needs of each specific patient. In this framework, the SPES research activities are focused on the innovative theranostic radionuclides ⁶⁷Cu, ⁴⁷Sc, ¹⁵⁵Tb, and ¹¹¹Ag, in addition to the ones useful for imaging (^99mTc and ⁵²Mn), fostering the preclinical and clinical studies in this field. These research activities are carried out thanks to a wide national and international network of collaborations with many Italian Universities (such as Ferrara, Milano, Padova and many others), the CNR in Milano, the LENA laboratory (Pavia), the Istituto Oncologico Veneto IOV_IRCCS (Padova), the Sacro Cuore Don Calabria hospital (Negrar, Verona), the Policlinico Sant’Orsola Malpighi (Bologna), the Cannizzaro hospital (Catania), the Bambin Gesù hospital (Roma) and other Italian research centres. The strategy of INFN-LNL through SPES facility is to enhance the R&D output for theranostics in one hand and to provide radiopharmaceuticals based on these innovative radionuclides to the medical sector in a joint venture with private and public related initiatives.
The SPES facility will thus contribute, with both described methods, to the development of new medically relevant radionuclides, with specific chemical-physical characteristics, to obtain innovative radiopharmaceuticals able to meet the requirements of each specific patient, an important step towards personalized medicine, that can be resumed with the well-known sentence about the five-“right”: The right patient, the right drug, the right dose, the right route and the right time.

Figure 1. Outline of the SPES infrastructures dedicated to medical radionuclides production at the INFN-LNL.

Gaia Pupillo, INFN Legnaro National Laboratories, ORCID id: 0000-0001-8731-7059

Bio: I’m a INFN researcher in the field of medical radionuclides production using accelerators and currently responsible of the “SPES_MED” project at the INFN-LNL. My research activity is mainly focused on cross section measurements of unexplored nuclear reactions, to find out possible new production routes for emerging radionuclides, with particular attention to the theranostic ones or pairs. Since my PhD in physics I am working at LARAMED, also coordinating INFN projects funded by CSN5 and CSN3; in these 10 years I collaborated with the Radioisotope Production and Radiation Technology Section of the International Atomic Energy Agency (IAEA, Wien). I participate in the INFN 4 Life Science committee, funded in 2021.