The widespread availability of novel radioactive isotopes showing nuclear characteristics suitable for diagnostic and therapeutic applications in nuclear medicine (NM) has experienced a great development in the last years, particularly as a result of key advancements of cyclotron-based radioisotope production technologies. At Legnaro National Laboratories of the National Institute of Nuclear Physics (LNL-INFN), Italy, a 70-MeV high current cyclotron has been recently installed. This cyclotron will be dedicated not only to pursuing fundamental nuclear physics studies, but also to research related to other scientific fields with an emphasis on medical applications. LARAMED project was established a few years ago at LNL-INFN as a new research line aimed at exploiting the scientific power of nuclear physics for developing innovative applications to medicine. The goal of this program is to elect LNL as a worldwide recognized hub for the development of production methods of novel medical radionuclides, still unavailable for the scientific and clinical community. Although the research facility is yet to become fully operative, the LARAMED team has already started working on the cyclotron production of conventional medical radionuclides, such as Tc-99m, and on emerging radionuclides of high potential medical interest, such as Cu-67, Sc-47, and Mn-52.

Technetium-99m (^99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. ^99mTc is typically extracted from portable generators containing ⁹⁹Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant ^99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the ¹⁰⁰Mo(p,2n)^99mTc reaction is considered one of the most promising routes for direct ^99mTc production in order to mitigate potential ⁹⁹Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm²) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H₂O₂.

Zirconium-89 (⁸⁹Zr) is an emerging radionuclide for positron emission tomography (PET), with nuclear properties suitable for imaging slow biological processes in cellular targets. The ⁸⁹Y(p,n)⁸⁹Zr nuclear reaction is commonly exploited as the main production route with medical cyclotrons accelerating low-energy (< 20 MeV) and low-current (< 100 μA) proton beams. Usually, natural yttrium solid targets manufactured by different methods, including yttrium electrodeposition, yttrium sputtering, compressed yttrium powders, and foils, were employed. In this study, the Spark Plasma Sintering (SPS) technique has been investigated, for the first time, to manufacture yttrium solid targets for an efficient ⁸⁹Zr radionuclide yield. The natural yttrium disc was bonded to a niobium backing plate using a commercial SPS apparatus and a prototype machine assembled at the University of Pavia. The resulting targets were irradiated in a TR19 cyclotron with a 12 MeV proton beam at 50 μA. A dedicated dissolution module, obtained from a commercial system, was used to develop an automated process for the purification and recovery of the produced ⁸⁹Zr radionuclide. The production yield and recovery efficiency were measured and compared to ⁸⁹Zr produced by irradiating standard yttrium foils. SPS manufactured targets withstand an average heat power density of approximately 650 W∙cm^-2 for continuous irradiation up to 5 h without visible damage. A saturation yield of 14.12 ± 0.38 MBq/μAh was measured. The results showed that the obtained ⁸⁹Zr production yield and quality were comparable to similar data obtained using standard yttrium foil targets. In conclusion, the present work demonstrates that the SPS technique might be a suitable technical manufacturing solution aimed at high-yield ⁸⁹Zr radioisotope production.

Magnetron sputtering is proposed here as an innovative method for the deposition of a material layer onto an appropriate backing plate for cyclotron solid targets aimed at medical radioisotopes production. In this study, a method to deposit thick, high-density, high-thickness-uniformity, and stress-free films of high adherence to the backing was developed by optimizing the fundamental deposition parameters: sputtering gas pressure, substrate temperature, and using a multilayer deposition mode, as well. This method was proposed to realize Mo-100 and Y-nat solid targets for biomedical cyclotron production of Tc-99m and Zr-89 radionuclides, respectively. The combination of all three optimized sputtering parameters (i.e., 1.63 × 10⁻² mbar Ar pressure, 500 °C substrate temperature, and the multilayer mode) allowed us to achieve deposition thickness as high as 100 µm for Mo targets. The 50/70-µm-thick Y targets were instead realized by optimizing the sputtering pressure only (1.36 × 10⁻² mbar Ar pressure), without making use of additional substrate heating. These optimized deposition parameters allowed for the production of targets by using different backing materials (e.g., Mo onto copper, sapphire, and synthetic diamond; and Y onto a niobium backing). All target types tested were able to sustain a power density as high as 1 kW/cm² provided by the proton beam of medical cyclotrons (15.6 MeV for Mo targets and 12.7 MeV for Y targets at up to a 70-µA proton beam current). Both short- and long-time irradiation tests, closer to the real production, have been realized.