Purpose: 64 Cu and 67 Cu radioisotopes have nuclear characteristics suitable for nuclear medicine applications. The production of 64 Cu is already well established. However, the production of 67 Cu in quantities suitable to conduct clinical trials is more challenging as it leads to the coproduction of other Cu isotopes, in particular 64 Cu. The aim of this study is to investigate the possibility of using a CuCl2 solution with a mixture of 67/64 Cu 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) 70 Zn in the energy range 70-45 MeV; (ii) 68 Zn in the energy range 70-35 MeV; (iii) a combination of 70 Zn (70-55 MeV) and 68 Zn (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 67/64 CuCl2 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 67/64 Cu mixture and to calculate the absorbed dose of self-irradiation. The biological damage produced by 67 Cu and 64 Cu 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 67 CuCl2 are higher than those of 64 CuCl2 . Absorbed dose values per unit of administered activity of 67/64 CuCl2 mixture increase with time after the EOB because the amount of 67 Cu in the mixture increases. Survival data showed that the biological damage caused per each decay of 67 Cu is greater than that of 64 Cu, assuming that radionuclides remain accumulated in the cell cytoplasm. Sphere model calculations demonstrated that 64 Cu administered activity must be about five times higher than that of 67 Cu 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 64 CuCl2 -absorbed dose to healthy organs will reach higher values than those of 67 CuCl2 . The supplemental activity of the 67/64 CuCl2 mixture, required to get the same tumor-absorbed dose produced by 67 CuCl2 , triggers a dose increment (DI) in healthy organs. The waiting time post-EOB necessary to keep this DI below 10% (t10% ) depends on the irradiation methods employed for the production of the 67/64 CuCl2 mixture.
Conclusions: A mixture of cyclotron produced 67/64 Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl2 with minimal DI to healthy organs compared with pure 67 Cu. Irradiation of a 70 Zn+68 Zn 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 t10% (10 h), and less than 1% of 61 Cu and 60 Cu impurities.
Keywords: 67CuCl2; copper radioisotope mixture; copper radioisotope production; cyclotron physics/radionuclide production; internal dosimetry; radiation dosimetry and risk; theranostic copper radioisotopes.
© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.