Cargando…
A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation
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 coproduct...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305914/ https://www.ncbi.nlm.nih.gov/pubmed/35134261 http://dx.doi.org/10.1002/mp.15524 |
_version_ | 1784752432399515648 |
---|---|
author | De Nardo, Laura Pupillo, Gaia Mou, Liliana Esposito, Juan Rosato, Antonio Meléndez‐Alafort, Laura |
author_facet | De Nardo, Laura Pupillo, Gaia Mou, Liliana Esposito, Juan Rosato, Antonio Meléndez‐Alafort, Laura |
author_sort | De Nardo, Laura |
collection | PubMed |
description | 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 CuCl(2) 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 CuCl(2) published by ICRP 53. The total absorbed dose generated by the (67/64)CuCl(2) 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)CuCl(2) are higher than those of (64)CuCl(2). Absorbed dose values per unit of administered activity of (67/64)CuCl(2) 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)CuCl(2)‐absorbed dose to healthy organs will reach higher values than those of (67)CuCl(2). The supplemental activity of the (67/64)CuCl(2) mixture, required to get the same tumor‐absorbed dose produced by (67)CuCl(2), 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)CuCl(2) mixture. CONCLUSIONS: A mixture of cyclotron produced (67/64)Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl(2) 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. |
format | Online Article Text |
id | pubmed-9305914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93059142022-07-28 A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation De Nardo, Laura Pupillo, Gaia Mou, Liliana Esposito, Juan Rosato, Antonio Meléndez‐Alafort, Laura Med Phys COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY 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 CuCl(2) 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 CuCl(2) published by ICRP 53. The total absorbed dose generated by the (67/64)CuCl(2) 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)CuCl(2) are higher than those of (64)CuCl(2). Absorbed dose values per unit of administered activity of (67/64)CuCl(2) 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)CuCl(2)‐absorbed dose to healthy organs will reach higher values than those of (67)CuCl(2). The supplemental activity of the (67/64)CuCl(2) mixture, required to get the same tumor‐absorbed dose produced by (67)CuCl(2), 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)CuCl(2) mixture. CONCLUSIONS: A mixture of cyclotron produced (67/64)Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl(2) 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. John Wiley and Sons Inc. 2022-02-20 2022-04 /pmc/articles/PMC9305914/ /pubmed/35134261 http://dx.doi.org/10.1002/mp.15524 Text en © 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY De Nardo, Laura Pupillo, Gaia Mou, Liliana Esposito, Juan Rosato, Antonio Meléndez‐Alafort, Laura A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title | A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title_full | A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title_fullStr | A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title_full_unstemmed | A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title_short | A feasibility study of the therapeutic application of a mixture of (67/64)Cu radioisotopes produced by cyclotrons with proton irradiation |
title_sort | feasibility study of the therapeutic application of a mixture of (67/64)cu radioisotopes produced by cyclotrons with proton irradiation |
topic | COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305914/ https://www.ncbi.nlm.nih.gov/pubmed/35134261 http://dx.doi.org/10.1002/mp.15524 |
work_keys_str_mv | AT denardolaura afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT pupillogaia afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT mouliliana afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT espositojuan afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT rosatoantonio afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT melendezalafortlaura afeasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT denardolaura feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT pupillogaia feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT mouliliana feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT espositojuan feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT rosatoantonio feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation AT melendezalafortlaura feasibilitystudyofthetherapeuticapplicationofamixtureof6764curadioisotopesproducedbycyclotronswithprotonirradiation |