Is the ⁶⁷Cu production worldwide feasible for expanding preclinical and clinical studies? How can we face the ingrowing demands of this emerging and promising theranostic radionuclide for personalized therapies? This review looks at the different production routes, including the accelerator- and reactor-based ones, providing a comprehensive overview of the actual ⁶⁷Cu supply, with brief insight into its use in non-clinical and clinical studies. In addition to the most often explored nuclear reactions, this work focuses on the ⁶⁷Cu separation and purification techniques, as well as the target material recovery procedures that are mandatory for the economic sustainability of the production cycle. The quality aspects, such as radiochemical, chemical, and radionuclidic purity, with particular attention to the coproduction of the counterpart ⁶⁴Cu, are also taken into account, with detailed comparisons among the different production routes. Future possibilities related to new infrastructures are included in this work, as well as new developments on the radiopharmaceuticals aspects.

The widespread availability of novel radioactive isotopes showing nuclear characteristics suitable for diagnostic and therapeutic applications in nuclear medicine (NM) has experienced a great development in the last years, particularly as a result of key advancements of cyclotron-based radioisotope production technologies. At Legnaro National Laboratories of the National Institute of Nuclear Physics (LNL-INFN), Italy, a 70-MeV high current cyclotron has been recently installed. This cyclotron will be dedicated not only to pursuing fundamental nuclear physics studies, but also to research related to other scientific fields with an emphasis on medical applications. LARAMED project was established a few years ago at LNL-INFN as a new research line aimed at exploiting the scientific power of nuclear physics for developing innovative applications to medicine. The goal of this program is to elect LNL as a worldwide recognized hub for the development of production methods of novel medical radionuclides, still unavailable for the scientific and clinical community. Although the research facility is yet to become fully operative, the LARAMED team has already started working on the cyclotron production of conventional medical radionuclides, such as Tc-99m, and on emerging radionuclides of high potential medical interest, such as Cu-67, Sc-47, and Mn-52.

New data for the ${}^{\text{nat}}\mathrm{V}(p,x)$ reactions have been measured in the range 26–70 MeV, with production of the nuclides ${}^{47}\mathrm{Sc}, {}^{43}\mathrm{Sc}, {}^{44m}\mathrm{Sc}, {}^{44g}\mathrm{Sc}, {}^{46}\mathrm{Sc}, {}^{48}\mathrm{Sc}, {}^{42}\mathrm{K}, {}^{43}\mathrm{K}, {}^{48}\mathrm{V}, {}^{48}\mathrm{Cr}, {}^{49}\mathrm{Cr}$, and ${}^{51}\mathrm{Cr}$. The focus is on the production of ${}^{47}\mathrm{Sc}$, a ${\beta }^{-}$ emitter suitable for innovative radiotheranostic applications in nuclear medicine. The measured cross sections for this radionuclide and its contaminants are compared with the theoretical excitation functions calculated with the talys code. In view of novel radiopharmaceutical applications, it is essential to accurately describe these cross sections for the evaluation of yields, purities, and dose releases. Hence, we optimize the level-density parameters of the microscopic models in the talys code to obtain the best possible descriptions of the new data. We consider different irradiation conditions to estimate the production yields from the cross sections determined in this paper.

Cyclotron-based radionuclides production by using solid targets has become important in the last years due to the growing demand of radiometals, e.g., ⁶⁸Ga, ⁸⁹Zr, ^43/47Sc, and ^52/54Mn. This shifted the focus on solid target management, where the first fundamental step of the radiochemical processing is the target dissolution. Currently, this step is generally performed with commercial or home-made modules separated from the following purification/radiolabelling modules. The aim of this work is the realization of a flexible solid target dissolution system to be easily installed on commercial cassette-based synthesis modules. This would offer a complete target processing and radiopharmaceutical synthesis performable in a single module continuously. The presented solid target dissolution system concept relies on an open-bottomed vial positioned upon a target coin. In particular, the idea is to use the movement mechanism of a syringe pump to position the vial up and down on the target, and to exploit the heater/cooler reactor of the module as a target holder. All the steps can be remotely controlled and are incorporated in the cassette manifold together with the purification and radiolabelling steps. The performance of the device was tested by processing three different irradiated targets under different dissolution conditions.

Purpose: ⁶⁴Cu and ⁶⁷Cu radioisotopes have nuclear characteristics suitable for nuclear medicine applications. The production of ⁶⁴Cu is already well established. However, the production of ⁶⁷Cu in quantities suitable to conduct clinical trials is more challenging as it leads to the coproduction of other Cu isotopes, in particular ⁶⁴Cu. The aim of this study is to investigate the possibility of using a CuCl₂ solution with a mixture of ^67/64Cu radioisotopes for therapeutic purposes, providing an alternative solution for the cyclotron production problem.Methods: Copper radioisotopes activities were calculated by considering proton beam irradiation of the following targets: (i) ⁷⁰Zn in the energy range 70–45 MeV; (ii) ⁶⁸Zn in the energy range 70–35 MeV; (iii) a combination of ⁷⁰Zn (70–55 MeV) and ⁶⁸Zn (55–35 MeV). The contribution of each copper radioisotope to the human‐absorbed dose was estimated with OLINDA/EXM software using the biokinetic model for CuCl₂ published by ICRP 53. The total absorbed dose generated by the ^67/64CuCl₂ mixture, obtained through different production routes, was calculated at different times after the end of the bombardment (EOB). A simple spherical model was used to simulate tumors of different sizes containing uniformly distributed ^67/64Cu mixture and to calculate the absorbed dose of self‐irradiation. The biological damage produced by ⁶⁷Cu and ⁶⁴Cu was also evaluated through cellular dosimetry and cell surviving fraction assessment using the MIRDcell code, considering two prostate cancer cell lines with different radiosensitivity.Results: The absorbed dose to healthy organs and the effective dose (ED) per unit of administered activity of ⁶⁷CuCl₂ are higher than those of ⁶⁴CuCl₂. Absorbed dose values per unit of administered activity of ^67/64CuCl₂ mixture increase with time after the EOB because the amount of ⁶⁷Cu in the mixture increases. Survival data showed that the biological damage caused per each decay of ⁶⁷Cu is greater than that of ⁶⁴Cu, assuming that radionuclides remain accumulated in the cell cytoplasm. Sphere model calculations demonstrated that ⁶⁴Cu administered activity must be about five times higher than that of ⁶⁷Cu to obtain the same absorbed dose for tumor mass between 0.01 and 10 g and about 10 times higher for very small spheres. Consequently, the ⁶⁴CuCl₂‐absorbed dose to healthy organs will reach higher values than those of ⁶⁷CuCl₂. The supplemental activity of the ^67/64CuCl₂ mixture, required to get the same tumor‐absorbed dose produced by ⁶⁷CuCl₂, triggers a dose increment (DI) in healthy organs. The waiting time post‐EOB necessary to keep this DI below 10% (t_10%) depends on the irradiation methods employed for the production of the ^67/64CuCl₂ mixture.Conclusions: A mixture of cyclotron produced ^67/64Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl₂ with minimal DI to healthy organs compared with pure ⁶⁷Cu. Irradiation of a ⁷⁰Zn+⁶⁸Zn target in the 70–35 MeV proton energy range for 185 h appears to be the best option from among all the production routes investigated, as it gives the maximum amount of activity, the shortest t_10% (10 h), and less than 1% of ⁶¹Cu and ⁶⁰Cu impurities.