Towards Ag-111 as a medical radionuclide: from production and laser photo-ionisation to cell dosimetry and radiation biophysics in the context of the ISOLPHARM project

The ISOLPHARM project, headed by the Legnaro National Laboratories (LNL) of the National Institute for Nuclear Physics (INFN), is aimed at the development of innovative radiopharmaceuticals for nuclear medicine. Therapeutic and diagnostic radionuclides will be produced employing the Isotope Separation On-Line (ISOL) technique at the SPES facility, nearing completion at INFN-LNL. Relying on a wide national network of INFN divisions, universities and hospitals, the ISOLPHARM collaboration has already begun a research campaign, involving also in vitro and in vivo preclinical trials, with the purpose of probing the therapeutic efficacy of radiopharmaceuticals loaded with the β− emitter Ag-111. In such a scenario, the aim of this thesis is to study the possible medical application of this nuclide at two levels: its production and its preclinical evaluation. From the former point of view, the focus is on the resonant laser photo-ionisation of Ag-111, which represents a crucial step in the production workflow, paying particular attention to offline experiments and theoretical modelling using the density matrix formalism. On the other hand, radiation biophysics experiments investigate for the first time the impact of Ag-111 on the survival of cancer cells; these activities are performed with the help of Geant4 Monte Carlo simulations for cellular dosimetry and of a novel biophysical model studying the behaviour of cell populations irradiated by radiopharmaceuticals.