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The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [ 111 In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.

Research in the field of radiopharmaceuticals is increasingly promoted by the widespread and growing interest in applying nuclear medicine procedures in both disease diagnosis and treatment. The production of radionuclides of medical interest is however a challenging issue. Along with the conventional techniques other innovative approaches are being investigated and, among those, the ISOLPHARM project is being developed at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). Such technique foresees the employment of the SPES ISOL facility to produce isobarically pure Radioactive Ion Beams (RIBs), obtained thanks to electromagnetic mass separation and collected on appropriate substrates. The latter are successively recovered and dissolved, allowing thus the chemical separation and harvesting of the nuclides of interest, free from any isotopic contaminant. Although ISOLPHARM can be potentially employed for most of the routinely used medical radioisotopes, its innovation potential is better expressed considering its capability to provide carrier free unconventional nuclides, difficult to produce with state-of-art techniques, such as 111 Ag, a β - emitter potentially interesting for therapeutic applications. Thus, in the framework of ISOLPHARM, INFN supported a two-years experiment, called ISOLPHARM_Ag, aimed at evaluating the feasibility of the production of a 111 Ag labelled radiopharmaceutical. The ISOL production yields are estimated by computing intensive Monte Carlo codes, that require an appropriate custom Information Technology infrastructure. The presented work is focused on the first part of the production chain including the capability to extract, ionize, and collect stable Ag beams with SPES technologies. MC calculations were used to estimate the expected 111 Ag in-target yields, whereas experiments with stable Ag were performed to test the ionization, transport and collection of Ag beams., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Radiopharmaceuticals represent a fundamental tool for nuclear medicine procedures, both for diagnostic and therapeutic purposes. The present work aims to explore the Isotope Separation On-Line (ISOL) technique for the production of carrier-free radionuclides for nuclear medicine at SPES, a nuclear physics facility under construction at INFN-LNL. Stable ion beams of strontium, yttrium and iodine were produced using the SPES test bench (Front-End) to simulate the production of 89 Sr, 90 Y, 125 I and 131 I and collected with good efficiency on suitable targets., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The ISOLPHARM project explores the feasibility of exploiting an innovative technology to produce extremely high specific activity beta-emitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals that are virtually mainly impossible to obtain in standard production facilities, at lower cost and with less environmental impact than traditional techniques. The groundbreaking ISOLPHARM method investigated in this project has been granted an international patent (INFN). As a component of the SPES (Selective Production of Exotic Species) project at the Istituto Nazionale di Fisica Nucleare–Laboratori Nazionali di Legnaro (INFN–LNL), a new facility will produce radioactive ion beams of neutron-rich nuclei with high purity and a mass range of 80–160 amu. The radioactive isotopes will result from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a target of UCx. The uranium in the target material will be 238U, yielding radioactive isotopes that belong to elements with an atomic number between 28 and 57. Isotope separation on line (ISOL) is adopted in the ISOLPHARM project to obtain pure isobaric beams for radiopharmaceutical applications, with no isotopic contaminations in the beam or subsequent trapping substrate. Isobaric contaminations may potentially affect radiochemical and radionuclide purity, but proper methods to separate chemically different elements can be developed. [ABSTRACT FROM AUTHOR]