A. Andrighetto's research while affiliated with INFN - Istituto Nazionale di Fisica Nucleare and other places

A two-step resonance photo-ionization scheme has been used to ionize samarium atoms in the SPES tantalum hot-cavity ion source. The effect of the ion load on the ion beam time structure and the laser enhancement of the ion yield has been studied at different ion source temperatures. Generally, the introduction of more positive ions (ion load) affects negatively the overall confinement of the laser ions inside the volume of the ion source. Possible enhancement of the laser ion confinement through the introduction of neutrals is observed as well. The ion load is also observed to affect the confinement in the transfer line much more than in the hot cavity. Measurement of the time structure with inverted polarity of the cavity DC heating supply confirmed the significance of the longitudinal potential for ion extraction. The laser enhancements of the ion yield are found to be sensitive to the ion load at low operating temperature of the ion source i.e. 1800°C, whereas at 2050°C and 2200°C, they are relatively stable till an ion load value of 1.2 µA.

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

The SPES laser ion source has been tested at ISOLDE Offline 2, CERN. A two-step single resonance photoionization scheme has been used to ionize gallium atoms in the SPES tantalum hot-cavity ion source. The ion beam time structure, laser enhancement of ion yield, and ionization efficiency are investigated in relation to the ion source temperature and ion load. From the time structures, it is inferred that a significant fraction of the extracted ions are generated in the transfer line rather than just in the hot cavity. The effect of the electrostatic axial field on the movement of ions inside the ion source is discussed. Generally, there is an inverse relationship between total ion load and the laser enhancement factor. This dependency is enhanced at lower operating temperature of the ion source. This is explained by the influence of thermionic electron emission and ion density on the transverse laser-ion confinement, and therefore the survival of ions as they drift towards the extraction region of the ion source. At 2200 ◦C, the nominal temperature for on-line operation of the ion source, the ratio of laser-ionized to surface-ionized gallium was stable around 55 during the measurement campaign, and independent of the total extracted ion current up to the measured value of 1.1 μA. A resonance laser ionization efficiency value of 27.2% for gallium has been measured

At the SPES (Selective Production of Exotic Species) facility, intense Radioactive Ion Beams (RIBs) are produced by the interaction of a 40 MeV proton beam with a multi-foil uranium carbide target employing the Isotope Separation On-Line (ISOL) technique. The Target Ion Source (TIS) unit constitutes the core of the isotope production process. TIS units are replaced on a periodic basis during operation to maintain high performance. An automated storage system has been designed to accept highly radioactive TIS units and house them during a cooling period prior to decommissioning. The system is conceived to meet strict functional and safety requirements. Its peculiar design allows for improved reliability and availability during critical operations, as well as minimization of staff exposure to ionizing radiation during maintenance tasks. This contribution describes the design and control architecture of the Temporary Storage System (TSS). The equipment is part of a structured framework of remote manipulation, consisting of various machines interlocked with the Access Control System (ACS) and the Machine Protection System (MPS).

Background Silver-111 is a promising β⁻-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the positron-emitting counterpart silver-103, thus imparting a truly theranostic potential to this element. A so-fitting matching pair could potentially overcome the current limitations associated with the forced use of chemically different isotopes as imaging surrogates of lutetium-177, leading to more accurate and efficient diagnosis and treatment. However, the use of silver-111-based radiopharmaceuticals in vivo has faced obstacles due to the challenges related to its production and radiochemical separation from the target material. To address these issues, this study aims to implement a chromatographic separation methodology for the purification of reactor-produced silver-111. The ultimate goal is to achieve a ready-to-use formulation for the direct radiolabeling of tumour-seeking biomolecules. Results A two-step sequence chromatographic process was validated for cold Ag-Pd separation and then translated to the radioactive counterpart. Silver-111 was produced via the ¹¹⁰Pd(n,γ)¹¹¹Pd nuclear reaction on a natural palladium target and the subsequent β⁻-decay of palladium-111. Silver-111 was chemically separated from the metallic target via the implemented chromatographic process by using commercially available LN and TK200 resins. The effectiveness of the separations was assessed by inductively coupled plasma optical emission spectroscopy and γ-spectrometry, respectively, and the Ag⁺ retrieval was afforded in pure water. Recovery of silver-111 was > 90% with a radionuclidic purity > 99% and a separation factor of around 4.21·10⁻⁴. Conclusions The developed separation method was suitable to obtain silver-111 with high molar activity in a ready-to-use water-based formulation that can be directly employed for the labeling of radiotracers. By successfully establishing a robust and efficient production and purification method for silver-111, this research paves the way for its wider application in targeted radionuclide therapy and precision imaging.

The production of medical radionuclides is one of the research activities carried out in the framework of the SPES (Selective Production of Exotic Species) project under the completion stage at the Legnaro National Laboratories of the National Institute for Nuclear Physics (INFN-LNL). The heart of SPES is the 70-MeV proton cyclotron having a dual-beam extraction, installed and commissioned in a new building equipped with ancillary laboratories currently under construction. The SPES main goal is the realization of an advanced ISOL (Isotope Separation On-Line) facility to produce re-accelerated exotic ion beams for fundamental nuclear physics studies. The cyclotron double-beam extraction system allows to simultaneously carry out applied research, such as radionuclides production for medicine (SPES- $$\gamma$$ γ ). This paper summarizes the results obtained with the interdisciplinary projects LARAMED (LAboratory of RAdionuclides for MEDicine) and ISOLPHARM (ISOL technique for radioPHARMaceuticals). The first one, based upon the direct activation method, is focused on the production of the radionuclides under the spotlight of the international community (e.g., $$^{99m}$$ 99 m Tc, $$^{67}$$ 67 Cu, $$^{52/51}$$ 52 / 51 Mn, $$^{47}$$ 47 Sc and Tb isotopes), from the nuclear cross-section measurements up to the preclinical studies. The other one exploits the ISOL technique for the development and production of radioisotopes with high-specific activity, such as $$^{111}$$ 111 Ag, going beyond the state of the art in the field. The most recent SPES- $$\gamma$$ γ research activities and future perspective are here described, characterized by a consolidated network of collaborations with national and international institutions.

Background: Silver-111 is a promising β⁻-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the positron-emitting counterpart silver-103, thus imparting a truly theranostic potential to this element. A so-fitting matching pair could potentially overcome the current limitations associated with the forced use of chemically different isotopes as imaging surrogates of lutetium-177, leading to more accurate and efficient diagnosis and treatment. However, the diffusion of silver-111 in vivo applications has been hindered so far by the challenges related to its production and radiochemical separation from the target material. To address these issues, this study aims to implement a chromatographic methodology for the purification of reactor-produced silver-111. The ultimate goal is to achieve a ready-to-use formulation for the direct radiolabeling of tumour-seeking biomolecules. Results: A two-step sequence chromatographic process was validated for cold Ag-Pd separation and then translated to the radioactive counterpart. Silver-111 was produced via the ¹¹⁰Pd(n,γ)¹¹¹Pd nuclear reaction on the palladium target and the subsequent β⁻-decay of palladium-111. Silver-111 was chemically separated from the metallic target via the implemented chromatographic process by using commercially available LN and TK200 resins. The effectiveness of the separations was assessed by inductively coupled plasma optical emission spectroscopy and γ-spectrometry, respectively, and the Ag⁺ retrieval was afforded in pure water. Recovery of silver-111 was > 90% with a radionuclidic purity > 99%. Conclusions: The developed separation method was suitable to obtain silver-111 with high molar activity in a ready-to-use water-based formulation that can be directly employed for the labeling of radiotracers. By successfully establishing a robust and efficient production and purification method for silver-111, this research paves the way for its wider application in targeted radionuclide therapy and precision imaging.