Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging
<b>Background:</b> While gallium-68 has traditionally dominated PET imaging in oncology, copper radionuclides have sparked interest for their potential applications in nuclear medicine and theranostics. Considering the advantageous physical decay properties of copper-61 compared to those...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/4/469 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849713560426381312 |
|---|---|
| author | Diana Rodrigues Alexandra I. Fonseca Sérgio do Carmo José Sereno Ivanna Hrynchak João N. Moreira Célia Gomes Antero Abrunhosa |
| author_facet | Diana Rodrigues Alexandra I. Fonseca Sérgio do Carmo José Sereno Ivanna Hrynchak João N. Moreira Célia Gomes Antero Abrunhosa |
| author_sort | Diana Rodrigues |
| collection | DOAJ |
| description | <b>Background:</b> While gallium-68 has traditionally dominated PET imaging in oncology, copper radionuclides have sparked interest for their potential applications in nuclear medicine and theranostics. Considering the advantageous physical decay properties of copper-61 compared to those of gallium-68, we describe a fully automated GMP-compliant synthesis process for <sup>61</sup>Cu-based radiopharmaceuticals and demonstrate their in vivo application for targeting the overexpressed PSMA by PET/MR imaging. <b>Methods:</b> Copper-61 was obtained through the irradiation of natural zinc liquid targets in a biomedical cyclotron. [<sup>61</sup>Cu]Cu-DOTAGA-PSMA-I&T and [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T were produced without manual intervention in two Synthera<sup>®</sup> Extension modules. Radiochemical purity was analyzed by radio-HPLC and iTLC. Cellular uptake was evaluated in LNCaP and DU145 cells. In vivo PET/MRI was performed in control mice to evaluate the biodistribution of both radiopharmaceuticals, and in tumor-bearing mice to assess the targeting ability towards PSMA. <b>Results:</b> The fully automated process developed proved to be effective for the synthesis of <sup>61</sup>Cu-based radiopharmaceuticals, with appropriate molar activities. The final products exhibited high radiochemical purity (>98%) and remained stable for up to 6 h after the EOS. A time-dependent increase in cellular uptake was observed in LNCaP cells, but not in DU145 cells. As opposed to [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T, [<sup>61</sup>Cu]Cu-DOTAGA-PSMA-I&T exhibited poor kinetic stability in vivo. Subsequent PET/MR imaging with [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T showed tumor uptake lasting up to 4 h post-injection, predominant renal clearance, and no detectable accumulation in non-targeted organs. <b>Conclusions:</b> These results demonstrate the feasibility of the implemented process, which yields adequate amounts of high-quality radiopharmaceuticals and can be adapted to any standard production facility. This streamlined approach enhances reproducibility and scalability, bringing copper-61 closer to widespread clinical use, to the detriment of the conventionally accepted gallium-68. |
| format | Article |
| id | doaj-art-c38cb578118f42dba48f56e6b2d1891e |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-c38cb578118f42dba48f56e6b2d1891e2025-08-20T03:13:55ZengMDPI AGPharmaceuticals1424-82472025-03-0118446910.3390/ph18040469Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer ImagingDiana Rodrigues0Alexandra I. Fonseca1Sérgio do Carmo2José Sereno3Ivanna Hrynchak4João N. Moreira5Célia Gomes6Antero Abrunhosa7Coimbra Institute for Biomedical Imaging and Translational Research, and Institute for Nuclear Sciences Applied to Health (CIBIT/ICNAS), University of Coimbra, 3000-548 Coimbra, PortugalICNAS Pharma, University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Biomedical Imaging and Translational Research, and Institute for Nuclear Sciences Applied to Health (CIBIT/ICNAS), University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Biomedical Imaging and Translational Research, and Institute for Nuclear Sciences Applied to Health (CIBIT/ICNAS), University of Coimbra, 3000-548 Coimbra, PortugalICNAS Pharma, University of Coimbra, 3000-548 Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, PortugalCentre for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Biomedical Imaging and Translational Research, and Institute for Nuclear Sciences Applied to Health (CIBIT/ICNAS), University of Coimbra, 3000-548 Coimbra, Portugal<b>Background:</b> While gallium-68 has traditionally dominated PET imaging in oncology, copper radionuclides have sparked interest for their potential applications in nuclear medicine and theranostics. Considering the advantageous physical decay properties of copper-61 compared to those of gallium-68, we describe a fully automated GMP-compliant synthesis process for <sup>61</sup>Cu-based radiopharmaceuticals and demonstrate their in vivo application for targeting the overexpressed PSMA by PET/MR imaging. <b>Methods:</b> Copper-61 was obtained through the irradiation of natural zinc liquid targets in a biomedical cyclotron. [<sup>61</sup>Cu]Cu-DOTAGA-PSMA-I&T and [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T were produced without manual intervention in two Synthera<sup>®</sup> Extension modules. Radiochemical purity was analyzed by radio-HPLC and iTLC. Cellular uptake was evaluated in LNCaP and DU145 cells. In vivo PET/MRI was performed in control mice to evaluate the biodistribution of both radiopharmaceuticals, and in tumor-bearing mice to assess the targeting ability towards PSMA. <b>Results:</b> The fully automated process developed proved to be effective for the synthesis of <sup>61</sup>Cu-based radiopharmaceuticals, with appropriate molar activities. The final products exhibited high radiochemical purity (>98%) and remained stable for up to 6 h after the EOS. A time-dependent increase in cellular uptake was observed in LNCaP cells, but not in DU145 cells. As opposed to [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T, [<sup>61</sup>Cu]Cu-DOTAGA-PSMA-I&T exhibited poor kinetic stability in vivo. Subsequent PET/MR imaging with [<sup>61</sup>Cu]Cu-NODAGA-PSMA-I&T showed tumor uptake lasting up to 4 h post-injection, predominant renal clearance, and no detectable accumulation in non-targeted organs. <b>Conclusions:</b> These results demonstrate the feasibility of the implemented process, which yields adequate amounts of high-quality radiopharmaceuticals and can be adapted to any standard production facility. This streamlined approach enhances reproducibility and scalability, bringing copper-61 closer to widespread clinical use, to the detriment of the conventionally accepted gallium-68.https://www.mdpi.com/1424-8247/18/4/469copper-61radiopharmaceuticalautomationpositron emission tomographyprostate cancerprostate specific membrane antigen |
| spellingShingle | Diana Rodrigues Alexandra I. Fonseca Sérgio do Carmo José Sereno Ivanna Hrynchak João N. Moreira Célia Gomes Antero Abrunhosa Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging Pharmaceuticals copper-61 radiopharmaceutical automation positron emission tomography prostate cancer prostate specific membrane antigen |
| title | Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging |
| title_full | Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging |
| title_fullStr | Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging |
| title_full_unstemmed | Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging |
| title_short | Is Copper-61 the New Gallium-68? Automation and Preclinical Proof-of-Concept of <sup>61</sup>Cu-Based Radiopharmaceuticals for Prostate Cancer Imaging |
| title_sort | is copper 61 the new gallium 68 automation and preclinical proof of concept of sup 61 sup cu based radiopharmaceuticals for prostate cancer imaging |
| topic | copper-61 radiopharmaceutical automation positron emission tomography prostate cancer prostate specific membrane antigen |
| url | https://www.mdpi.com/1424-8247/18/4/469 |
| work_keys_str_mv | AT dianarodrigues iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT alexandraifonseca iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT sergiodocarmo iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT josesereno iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT ivannahrynchak iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT joaonmoreira iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT celiagomes iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging AT anteroabrunhosa iscopper61thenewgallium68automationandpreclinicalproofofconceptofsup61supcubasedradiopharmaceuticalsforprostatecancerimaging |