Production of the PET radionuclide 61Cu via the 62Ni(p,2n)61Cu nuclear reaction

Santiago Andrés Brühlmann; Martin Walther; Klaus Kopka; Martin Kreller

doi:10.1186/s41181-023-00233-z

Production of the PET radionuclide ⁶¹Cu via the ⁶²Ni(p,2n)⁶¹Cu nuclear reaction

EJNMMI Radiopharm Chem. 2024 Jan 5;9(1):3. doi: 10.1186/s41181-023-00233-z.

Authors

Santiago Andrés Brühlmann^{1

2}, Martin Walther³, Klaus Kopka^{1

2

4

5}, Martin Kreller¹

Affiliations

¹ Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
² Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01062, Dresden, Germany.
³ Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany. m.walther@hzdr.de.
⁴ National Center for Tumor Diseases (NCT) Dresden, University Hospital Carl Gustav Carus, Fetscherstraße 74, 01307, Dresden, Germany.
⁵ German Cancer Consortium (DKTK), Partner Site Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Abstract

Background: There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio ⁶¹Cu, ⁶⁴Cu and ⁶⁷Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide physical half-lives. Due to the high availability of ⁶⁴Cu, its translation into the clinic is being successfully carried out, giving the example of the FDA approved radiopharmaceutical Detectnet (copper Cu 64 dotatate injection). However, a shorter-lived PET radionuclide such as ⁶¹Cu may as well be beneficial.

Results: Proton irradiation of enriched ⁶²Ni electrodeposited targets with a compact cyclotron produced the desired radionuclide via the ⁶²Ni(p,2n)⁶¹Cu nuclear reaction, leading to ⁶¹Cu activities of up to 20 GBq at end of bombardment and 8 GBq at end of purification. Furthermore, two purification methods are compared leading to comparable results regarding separation yield and product purity. Following the radiochemical separation, quality assessment of this product [⁶¹Cu]CuCl₂ solution proved radionuclidic purities (RNP) over 99.6% and apparent molar activities (AMA) of 260 GBq/µmol with the 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA) chelator, end of purification corrected.

Conclusions: In the current article a comprehensive novel production method for the PET radionuclide ⁶¹Cu is presented, providing an alternative to the most popular production routes. Characterization of the [⁶¹Cu]CuCl₂ product showed both high RNP as well as high AMA, proving that the produced activity presented high quality regarding radiolabeling up to 9 h after end of purification. Furthermore, production scalability could be easily achieved by increasing the irradiation time.

Keywords: Copper-61; CopperNostics; PET; Radiocopper; Target chemistry; Targetry; Theranostics.