Alternative routes for 64Cu production using an 18 MeV medical cyclotron in view of theranostic applications

Abstract

Radiometals play a fundamental role in the development of personalized nuclear medicine. In particular, copper radioisotopes are attracting increasing interest since they offer a varying range of decay modes and half-lives and can be used for imaging (⁶⁰Cu, ⁶¹Cu, ⁶²Cu and ⁶⁴Cu) and targeted radionuclide therapy (⁶⁴Cu and ⁶⁷Cu), providing two of the most promising true theranostic pairs, namely ⁶¹Cu/⁶⁷Cu and ⁶⁴Cu/⁶⁷Cu. Currently, the most widely used in clinical applications is ⁶⁴Cu, which has a unique decay scheme featuring β⁺-, β^--decay and electron capture. These characteristics allow its exploitation in both diagnostic and therapeutic fields. However, although ⁶⁴Cu has extensively been investigated in academic research and preclinical settings, it is still scarcely used in routine clinical practice due to its insufficient availability at an affordable price. In fact, the most commonly used production method involves proton irradiation of enriched ⁶⁴Ni, which has a very low isotopic abundance and is therefore extremely expensive. In this paper, we report on the study of two alternative production routes, namely the ⁶⁵Cu(p,pn)⁶⁴Cu and ⁶⁷Zn(p, α)⁶⁴Cu reactions, which enable low and high ⁶⁴Cu specific activities, respectively. To optimize the ⁶⁴Cu production, while minimizing the mass of copper used as a target in the first case, or the co-production of other copper radioisotopes in the second case, an accurate knowledge of the production cross sections is of paramount importance. For this reason, the involved nuclear reaction cross sections were measured at the Bern medical cyclotron laboratory by irradiating enriched ⁶⁵CuO and enriched ⁶⁷ZnO targets. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. Several production tests were performed to confirm these findings.