**1. Introduction**

Copper-67 (67Cu) (t1/2 = 2.58 d), the longest-living radioisotope of Cu, is of paramount importance because of its simultaneous emissions of β − radiation (mean β − energy: 141 keV; Eβ−max: 562 keV), useful for therapeutic treatments and γ-rays (93 and 185 keV), suitable for single-photon emission computed tomography (SPECT) imaging. In fact, the <sup>67</sup>Cu mean β <sup>−</sup>-emission energy of 141 keV (Eβ−max: 562 keV) is slightly higher than that of Lutetium-177 (177Lu, β <sup>−</sup>-emission energy of 133.6 keV, Eβ−max: 497 keV). <sup>67</sup>Cu decay characteristics make it one of the most promising theranostic radionuclides and its long half-life makes it suitable for imaging in vivo slow pharmacokinetics, such as monoclonal antibodies (MoAbs) or large molecules [1]. <sup>67</sup>Cu, studied for decades for radioimmunotherapy [2–4], is currently under the spotlight in the international community, as highlighted by the recent IAEA Coordinated Research Project (CRP) on "Therapeutic Radiopharmaceuticals Labelled with New Emerging Radionuclides (67Cu, <sup>186</sup>Re, <sup>47</sup>Sc)" (IAEA CRP no. F22053) [5,6]. <sup>67</sup>Cu can also be paired with the β + emitters <sup>64</sup>Cu, <sup>61</sup>Cu, and <sup>60</sup>Cu to perform pretherapy biodistribution determinations and dosimetry using positron emission tomography (PET) systems. Table 1 presents the decay characteristics of <sup>67</sup>Cu and 64/61/60Cu-radionuclides, as extracted from the NuDat 3.0 database [7].

Among copper radionuclides, only <sup>64</sup>Cu has been widely used for preclinical and clinical PET studies due to its moderate half-life (t1/2 = 12.7 h), low positron energy, and availability [8]. Given that copper radioisotopes are chemically identical, the same bifunctional chelators that have been developed for <sup>64</sup>Cu radiopharmaceuticals can be used directly for <sup>67</sup>Cu (and 61/60Cu) labeling. While the production techniques for <sup>64</sup>Cu are well

**Citation:** Mou, L.; Martini, P.; Pupillo, G.; Cieszykowska, I.; Cutler, C.S.; Mikołajczak, R. <sup>67</sup>Cu Production Capabilities: A Mini Review. *Molecules* **2022**, *27*, 1501. https:// doi.org/10.3390/molecules27051501

Academic Editor: Bohumír Gr˝uner

Received: 31 January 2022 Accepted: 18 February 2022 Published: 23 February 2022

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known and are usually based on the <sup>64</sup>Ni(p,n)64Cu, and <sup>64</sup>Ni(d,2n)64Cu reactions [9], the use of <sup>67</sup>Cu has been prevented by a lack of regular availability of sufficient quantities for preclinical and clinical studies. Only recently has <sup>67</sup>Cu become available in the U.S. through the Department of Energy Isotope Program (DOE-IP), in quantities and purities that are sufficient for medical research applications [10]. The investigation of <sup>67</sup>Cu supply worldwide is, therefore, a crucial point, and this review presents the state-of-art in <sup>67</sup>Cu production and medical applications.


**Table 1.** Main decay characteristics of <sup>67</sup>Cu and 64/61/60Cu-radionuclides [7].
