The use of radioisotopes in nuclear medicine applications became essential for the diagnosis and follow-up imaging of many oncological, cardiovascular, and neurodegenerative diseases, in a safe and non-invasive way. Their use in the personalized treatment of tumors is on the verge to change the oncological patient management. Optimization of the radioisotopes production aims to maximize the production efficiency while minimizing side reactions and costs. A practical approach to balance these non-converging ways is to employ the simulation tools in the process design phase and experimental setup. In this way, the production yield can be estimated and the radionuclide impurities content that appears during the bombardment of the target of interest can be optimally set below acceptable limits. Copper-64 is an emerging radionuclide in nuclear medicine theragnostic applications due to three decay modes, namely electron capture, electron (β⁻) and positron (β⁺) emissions, and a 12.7 h half-life, favorable for visualization of fast biological processes. Optimization of ⁶⁴Cu production by irradiation of enriched ⁶⁴Ni targets with protons in a particular geometry on a TR-19 cyclotron is discussed in this work. The simulated activity produced on different levels of enrichment of the ⁶⁴Ni targets was calculated using the Monte Carlo simulation in the Geant4 platform, where a customized solid target irradiation system set-up was replicated; the obtained parameters were implemented in the experiments and the results were compared, aiming to validate the simulation parameters through experimental data.As the simulated and experimental results regarding the production of ⁶⁴Cu via⁶⁴Ni(p,n)⁶⁴Cu reaction are in good compliance, the tool can be further applied for the optimization of the production of other radionuclides on the same set-up.

Zirconium-89 (⁸⁹Zr) is a highly valued diagnostic radionuclide for positron emission tomography (PET) due to its long physical half-life of 78.4 h and decay characteristics, being preferred for the radiolabelling of nanoparticles and slow kinetics macromolecules, such as antibodies. ⁸⁹Zr-based high-resolution PET images can be employed to scan tumours and localize the tracer on a longer timeframe, which allows for real-time therapy monitoring. The goal of this study was to maximize the ⁸⁹Zr production yield by fine-tunning the irradiation parameters of a solid target, in two different experimental set-ups, using a variable energy 14-19 MeV TR-19 cyclotron. Monte Carlo programs simulated the irradiation geometry and estimated the activity and irradiation yields produced by the ⁸⁹Y(p, n)⁸⁹Zr reaction, at the process optimal parameters. The resulted data were compared with the experimental data collected in our particular irradiation setups. ⁸⁹Zr was obtained from ^natY foil target using: (A) the solid target holder placed on the extraction port, and (B) the automated solid target irradiation station, installed on a sloped-down extension of the proton beamline. The two irradiation geometries are differentiated by the distances from the respective extraction ports, beam-geometry and shape, cooling capacity, and degrader's thickness. Based on the specific geometries, A and B, the Monte Carlo simulations output determined the optimal experimental irradiation parameters (extracted energy, degrader thickness, proton current intensity), as well as the target thickness. The 250 μm ^natY foils were irradiated with 14 MeV protons and an integrated current of 32 µA·h, on the solid target configuration A, and with 15.2 MeV protons, 100 µA·h on the solid target configuration B. After the dissolution and purification of the targets, [⁸⁹Zr]Zr-oxalate solutions of 1.28 ± 0.18 GBq, and 2.95 ± 0.31 GBq respectively, were evaluated, to determine the radionuclidic purity and contaminant levels of ⁸⁹Zr solutions across different incident proton beam energies. The pharmaceutical specifications require the solutions radionuclidic purity to be above 99.9% of the total radioactivity, as criteria of their suitability for use as radiopharmaceutical precursors for antibodies radiolabelling. Simulations were providing optimized input parameters to maximize the production yield of ⁸⁹Zr and subsequently, to achieve the highest possible activity with no detriment to radionuclide purity, as per the [⁸⁹Zr]Zr-oxalate solution pharmaceutical specification. The parameters were then implemented in the experiments, and the production processes were tested on two particular irradiation configurations. The yields and activities produced through ⁸⁹Y(p, n)⁸⁹Zr reaction, at the TR-19 cyclotron were in good agreement with the simulations, within 18.4-21.3%, which include activity losses during irradiation and post-processing and uncertainties resulted from activity measurements and cross-section values.

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [⁶⁴Cu]CuCl₂ solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [⁶⁴Cu]CuCl₂ solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 μAh led to 704 ± 84 MBq/μA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 μAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)_sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [⁶⁴Cu]CuCl₂ solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/μmol for LT route compared to 45 and 52 GBq/μmol for ST route, respectively). The strong interaction between the [⁶⁴Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data.