A New Production Method of High Specific Activity Radionuclides Towards Innovative Radiopharmaceuticals: The Isolpharm Project

Abstract

Radionuclides of interest in nuclear medicine are generally produced in cyclotrons or nuclear reactors, with associated issues such as highly enriched target costs and undesired contaminants. The ISOLPHARM project (ISOL technique for radioPHARMaceuticals) explores the feasibility of producing extremely high specific activity βemitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals very hardly obtained in standard production facilities. Radioactive isotopes will be obtained from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a UCx target. By means of: high working temperatures and high vacuum conditions, the migration of the radioactive elements towards an ion source, a potential difference up to 40 kV, and a mass separation device, an isobaric beam of desired radionuclides will be produced and implanted on a deposition target. The availability of innovative isotopes can potentially open a new generation of radiopharmaceuticals, based on nuclides never studied so far. Among these, a very promising isotope could be Ag-111, a βemitter with a half-life (7.45 d), an average βenergy of 360 keV, a tissue penetration of around 1 mm, and a low percentage of γ-emission. The proof of principle studies on Ag-111 production and radiolabeling are currently under investigation in the ISOLPHARM_EIRA project, where both its production and possible application as a radiopharmaceutical precursor will be evaluated in its computational/physics, radiochemistry, and radiobiology tasks. Currently, innovative macromolecules meeting the specific requirements for the chelation and targeted delivery of Ag-111 are being developed, which will be further tested in vitro on 2D and 3D models, as well as in vivo for their pharmacokinetics and therapeutic potential onto xenograft models.