**5. Conclusions**

This review reveals the international effort to supply <sup>67</sup>Cu, a promising theranostic radionuclide. The increasing availability of intense particle accelerators and the optimization of the associated technologies (targetry and radiochemical processing) are making <sup>67</sup>Cu closer to the clinics. The positron emitter counter-parts of <sup>67</sup>Cu, i.e., <sup>60</sup>Cu, <sup>61</sup>Cu, and <sup>64</sup>Cu, can be produced in cyclotrons. In particular, <sup>64</sup>Cu is now widely available for clinical use, promoting the development of innovative Cu-labeled radiopharmaceuticals. The improved availability of <sup>67</sup>Cu would speed up further radiopharmaceutical applications for therapy. Should <sup>67</sup>Cu be produced in sufficient quantities and quality, its clinical use would spread worldwide. Therefore, in addition to a detailed analysis of the possible nuclear reactions to produce <sup>67</sup>Cu, the radiochemical procedures to extract and purify Cu from the bulk material were also described in this work. Recent developments in the photoproduction of <sup>67</sup>Cu, and in the possibility of having accelerators providing intense 70 MeV proton beams and/or intense 30 MeV deuteron beams, are grounds for a future reliable supply of <sup>67</sup>Cu.

In most of the nuclear reactions leading to <sup>67</sup>Cu, the <sup>64</sup>Cu is produced in various radioactivity ratios. What is the impact of this impurity on a patient's dosimetry? Further studies on the possible use of 67/64Cu labeled-radiopharmaceuticals are encouraged, to find out the possible therapeutic benefits for the patient exploiting, at the same time, the β −

radiation emitted by <sup>67</sup>Cu and <sup>64</sup>Cu decay and the shorter range Auger-electrons emitted by <sup>64</sup>Cu. Encouraging technological achievements, namely working out methods to isolate the small amount of <sup>67</sup>Cu from the large mass of zinc in the target and to recover the target material in the accelerator-based production, show that, soon, <sup>67</sup>Cu will be available daily in the United States and in Europe for research purposes. The relatively long half-life of <sup>67</sup>Cu makes production in large facilities and the shipping of the purified product to clinical centers possible.

**Author Contributions:** Conceptualization, L.M., G.P., P.M., I.C. and R.M.; formal analysis, L.M. and G.P.; writing—original draft preparation, L.M., G.P., P.M., I.C. and R.M.; writing—review and editing, L.M., G.P., P.M., I.C., C.S.C. and R.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was partially supported by the IAEA/CRP code F22053; the Polish Ministry of Science and Higher Education, grant no. 3639/FAO/IAEA/16/2017/0; the CERAD project, financed under the Smart Growth Operational Programme 2014–2020, Priority IV, Measure 4.2. POIR.04.02.00– 14-A001/16; COME project INFN-CSN3; LARAMED and TERABIO premium projects funded by the Italian Ministry for University and Research (MIUR).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Acknowledgments:** We would like to acknowledge PRISMAP, the European medical radionuclide programme, for the production of high purity radionuclides (radioactive isotopes) by mass separation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101008571.

**Conflicts of Interest:** The authors declare no conflict of interest.
