Radio Pharmaceutical Therapy (RPT) comes forth as a promising technique to treat a wide range of tumors while ensuring low collateral damage to nearby healthy tissues. This kind of cancer therapy exploits the radiation following the decay of a specific radionuclide to deliver a lethal dose to tumor tissues. In the framework of the ISOLPHARM project of INFN, ¹¹¹Ag was recently proposed as a promising core of a therapeutic radiopharmaceutical. In this paper, the production of ¹¹¹Ag via neutron activation of ¹¹⁰Pd-enriched samples inside a TRIGA Mark II nuclear research reactor is studied. The radioisotope production is modeled using two different Monte Carlo codes (MCNPX and PHITS) and a stand-alone inventory calculation code FISPACT-II, with different cross section data libraries. The whole process is simulated starting from an MCNP6-based reactor model producing the neutron spectrum and flux in the selected irradiation facility. Moreover, a cost-effective, robust and easy-to-use spectroscopic system, based on a Lanthanum Bromo-Chloride (LBC) inorganic scintillator, is designed and characterized, with the aim of using it, in the future, for the quality control of the ISOLPHARM irradiated targets at the SPES facility of the Legnaro National Laboratories of INFN. ^natPd and ¹¹⁰Pd-enriched samples are irradiated in the reactor main irradiation facility and spectroscopically characterized using the LBC-based setup and a multiple-fit analysis procedure. Experimental results are compared with theoretical predictions of the developed models, showing that inaccuracies in the available cross section libraries prevent an accurate reproduction of the generated radioisotope activities. Nevertheless, models are normalized to our experimental data allowing for a reliable planning of the ¹¹¹Ag production in a TRIGA Mark II reactor.

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.

The ISOLPHARM project has the goal of producing innovative radiopharmaceuticals taking advantage of the radionuclides produced in the SPES ISOL facility, nearing completion at INFN-LNL. One of the main radionuclides of interest for the project is ¹¹¹Ag, which is a novel candidate for therapeutic and theranostic applications in nuclear medicine. Among the various steps of the ISOL technique, which stands for "Isotope Separation On-Line", the main stages contributing to selectivity are ionization and mass separation. In general, the latter ensures isotopic selectivity, while the former can be element-specific. In particular, the Laser Ion Source (LIS) is the one that guarantees the best selectivity, as it can provide to each element the precise energy required for ionization. Moreover, if narrowband lasers are available, the isotopic shift in one of the ionization steps can be used to tell apart different isotopes as well. The aim of this study is to assess, through the formalism of the reduced density matrix, the optimum laser power to maximize the ion yield and the isotopic selectivity of ¹¹¹Ag in the SPES online environment. Furthermore, other aspects affecting the yield, such as time delay, power broadening and Doppler broadening, are evaluated.

We report on a laser photo-ionization study of silver in relation to the Selective Production of Exotic Species (SPES) project at INFN-LNL in the off-line laser laboratory. In this study, two dye lasers and an ablation laser operating at 10 Hz are used alongside a time-of-flight mass spectrometer (TOF-MS). Isotopic separation of the natural, stable isotopes ${}^{107}$Ag and ${}^{109}$Ag was clearly observed in the TOF signal. Resonant photo-ionization of silver was achieved with the use of the scheme 4d${}^{10}$5s ${}^2$S${}_{1/2}$→ 4d${}^{10}$5p ${}^2$P${}_{3/2}^o$→ 4d${}^{10}$6d ${}^2$D${}_{3/2}$ with transition wavelengths of 328.163 nm and 421.402 nm, respectively. Doppler-suppressed spectroscopy of these transition lines was performed in an ablation plume. Doppler broadening with collinear injection of excitation lasers and the effect of the linewidths of the excitation lasers were investigated. The fine-structure splitting of the level 4d${}^{10}$6d ${}^2$D (J = 5/2 and J = 3/2) was confirmed to be 186 ± 2 pm, corresponding to 314 ± 3 GHz.

Targeted Radionuclide Therapy (TRT) is a well-established technique for cancer treatment. In this approach, radionuclides are bound to specific drugs that selectively transport them to the tumor site. Within the ISOLPHARM project, a radiopharmaceutical for TRT based on the innovative radionuclide ¹¹¹ Ag is currently under development. ¹¹¹ Ag has a half-life of 7.45 days and decays by emitting both electrons and gamma-rays. The emission of gamma-rays, predominantly at an energy of 342 keV, enables the visualization of ¹¹¹ Ag using a gamma camera. In this work, we describe a Monte Carlo simulation developed to optimize the design parameters of such an imaging device. The simulation is based on the Geant4 toolkit, which accurately models the interactions between particles and matter. The estimated spatial resolution and sensitivity of the system are approximately 4 mm and 19 cps/MBq, respectively. The simulated device is able to resolve lesions with a lesion-to-background activity ratio of 4:1 under in-vivo-like conditions. These results indicate that the proposed gamma camera can provide cost-effective imaging capabilities for preclinical radiopharmaceutical studies.

Targeted Radionuclide Therapy (TRT) is a medical technique exploiting radionuclides to combat cancer growth and spread. TRT requires a supply of radionuclides that are currently produced by either cyclotrons or nuclear research reactors. In this context, the ISOLPHARM project investigates the production of innovative radionuclides for medical applications. This production will be based on the forthcoming SPES facility at the Legnaro National Laboratories (LNL) of the National Institute for Nuclear Physics (INFN), an ISOL facility where high-purity radioactive beams will be used to produce carrier-free radiopharmaceuticals. Previous studies demonstrated that a significant amount of ¹¹¹Ag, an innovative β/γ emitter suitable for TRT with theranostic applications, can be obtained at the SPES facility. The present work describes the first imaging study on phantoms with ¹¹¹Ag performed by the ISOLPHARM collaboration. This is a fundamental step to pave the way for the upcoming in vivo studies on the ¹¹¹Ag-based radiopharmaceutical currently being developed. The imaging potential of this radionuclide was investigated by acquiring phantom images with Cerenkov Luminescence Imaging (CLI) and digital autoradiography (ARG).