Sustainable cyclotron production of copper radioisotopes through gallium recovery and zinc target recycling

The growing demand for medical radiometals calls for more sustainable production strategies that minimize waste and improve resource efficiency. Herein, we present a circular radiometal chemistry approach for the cyclotron-based production of copper radioisotopes using a medical cyclotron and natZnO targets. The workflow integrates irradiation, radiochemical separation, and material recovery within a closed-loop system inspired by the waste-as-resource principles. natZnO targets were produced using Spark Plasma Sintering and subsequently irradiated at 17.9 MeV, 20 μA for up to 1 h. Following proton irradiation and primary separation of the produced 61Cu (up to 969 MBq at the End Of Bombardment), co-produced gallium radioisotopes were successfully recovered from post-separation waste streams through a two-step chromatographic process, achieving 85% and 89% recovery yields for copper and gallium isotopes, respectively. Both the produced copper and gallium isotopes were successfully employed in radiolabeling and apparent molar activity (AMA) studies with radiopharmaceutical ligands, achieving AMA values of up to 3.55 GBq/μmol and 4.01 GBq/μmol for copper and gallium, respectively. In addition, targets produced from natZnO recovered via a precipitation-based method (recovery yield up to 85%) were successfully irradiated, confirming the feasibility of material reintegration into the production cycle. This work establishes a scalable proof-of-concept for a circular workflow in radiometal production by combining gallium recovery and zinc recycling. This approach reduces waste generation and improves possible utilization of enriched materials, resulting in a more sustainable access to emerging theranostic radionuclides such as copper and gallium radioisotopes.