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

Background: There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio Cu, Cu and Cu, 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 Cu, 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 Cu may as well be beneficial.

Results: Proton irradiation of enriched Ni electrodeposited targets with a compact cyclotron produced the desired radionuclide via the Ni(p,2n)Cu nuclear reaction, leading to Cu 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 [Cu]CuCl 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 Cu is presented, providing an alternative to the most popular production routes. Characterization of the [Cu]CuCl 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.