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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/4/469 |
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| Summary: | <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. |
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| ISSN: | 1424-8247 |