64 Cu production via the 68 Zn(p,nα) 64 Cu nuclear reaction: An untapped, cost-effective and high energy production route

Copper-64 ( Cu, t = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of Cu produced via the Zn(p,nα) Cu nuclear reaction. Macrocyclic chelators DOTA, NOTA, TETA, and prostate-specific membrane antigen ligand PSMA I&T were radiolabeled with purified Cu and tested for in vitro stability. [ Cu]Cu-PSMA I&T was used to demonstrate in vivo PET imaging using Cu synthesized via the Zn(p,nα) Cu production route and its suitability as a theranostic imaging partner alongside Cu therapy. Cu was produced on a 24 MeV TR-24 cyclotron at a beam energy of 23.5 MeV and currents up to 70 μA using 200 mg Zn encapsulated within an aluminum‑indium-graphite sealed solid target assembly. Cu semi-automated purification was performed using a NEPTIS Mosaic-LC synthesis unit employing CU, TBP, and TK201 (TrisKem) resins. Radionuclidic purity was measured by HPGe gamma spectroscopy, while ICP-OES assessed elemental purity. Radiolabeling was performed with NOTA at room temperature and DOTA, TETA, and PSMA I&T at 95 °C. Cu incorporation was studied by radio-TLC. Cu in vitro stability of [ Cu]Cu-NOTA, [ Cu]Cu-DOTA, [ Cu]Cu-TETA, and [ Cu]Cu-PSMA I&T was assessed at 37 °C from 0 to 72 h in human blood serum. Preclinical PET imaging was performed at 1, 24, and 48 h post-injection with [ Cu]Cu-PSMA I&T in LNCaP tumor-bearing mice and compared with [ Ga]Ga-PSMA I&T. Maximum purified activity of 4.9 GBq [ Cu]CuCl was obtained in 5 mL of pH 2-3 solution, with 2.9 GBq Cu concentrated in 0.5 mL. HPGe gamma spectroscopy of purified Cu detected