biostudies-literatureUnknown49(4)De Nardo LINFN CSN3 project COME - COpper MEasurement<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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% (t_10% ) depends on the irradiation methods employed for the production of the ^67/64 CuCl₂ mixture.<h4>Conclusions</h4>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 t_10% (10 h), and less than 1% of ⁶¹ Cu and ⁶⁰ Cu impurities.Medical physics2709-2724https://www.ebi.ac.uk/biostudies/studies/S-EPMC9305914biostudies-literatureA feasibility study of the therapeutic application of a mixture of ^67/64 Cu radioisotopes produced by cyclotrons with proton irradiation.PMC9305914Esposito JRosato ADe Nardo LMou LPupillo GMelendez-Alafort LfalseA feasibility study of the therapeutic application of a mixture of ^67/64 Cu radioisotopes produced by cyclotrons with proton irradiation.<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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% (t_10% ) depends on the irradiation methods employed for the production of the ^67/64 CuCl₂ mixture.<h4>Conclusions</h4>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 t_10% (10 h), and less than 1% of ⁶¹ Cu and ⁶⁰ Cu impurities.2022-01-01T00:00:00Z2022 Apr2025-04-04T12:26:47.916Z2022-08-03T07:07:14.795ZS-EPMC93059143513426110.1002/mp.15524