Fully automated, commercial cassette-based production of high-purity [64Cu]CuCl2 from solid Ni target

Introduction: Copper-64 (⁶⁴Cu) is an attractive radionuclide for nuclear medical imaging. This radionuclide decays with low energy positron emission (β⁺ 17.6%, E_avg = 653 keV) and intermediate half-life (t_1/2 = 12.7 h). ⁶⁴Cu is amenable for labelling both short (minutes) and long (hours/days) incubating biological vectors and is exemplified by the many reports of ⁶⁴Cu labelled small molecule, peptides, proteins and nanoparticles. Clinical studies with ⁶⁴Cu have also progressed significantly in the past two decades. This work focuses on obtaining high-purity [⁶⁴Cu]CuCl₂ via a cassette-based automated separation method using a one column approach implemented on the Taddeo-PRF chemistry platform.

Methods: ⁶⁴Ni is electroplated onto a target shuttle and irradiated with 14.4 MeV protons to produce ⁶⁴Cu. The irradiated target is dissolved and purified to obtain [⁶⁴Cu]CuCl₂. Two purification methods are tested on the ALCEO system (COMECER); 1. AG 1-X8 resin (Biorad); 2. TK201 resin (Triskem). ICP-MS has been performed to monitor the quality of [⁶⁴Cu]CuCl₂.

Results: ⁶⁴Cu is produced using the AG 1-X8 method with a yield of 2.49 ± 0.67 MBq/µAh/mg (N=21), electroplating 53.93 ± 20.42 mg of ⁶⁴Ni and bombarding at 35 ± 0.2 µA for 247.95 ± 74.74 minutes with a proton beam. For the TK201 method, the yield is 2.30 ± 0.83 MBq/µAh/mg (N=61), electroplating 69.50 ± 17.61 mg of ⁶⁴Ni and bombarding at 35 ± 0.2 µA for 201.13 ± 58.10 minutes. ICP-MS shows for the AG 1-X8 method (N=12): [Ni-64] 70728 ± 81643 ppb, [Cu] 1125 ± 657 ppb, [Fe] 8040 ± 4287 ppb, [Al] 3303 ± 1925 ppb, [Zn] 2336 ± 2602 ppb, [Co] 33 ± 35 ppb. Instead, for the TK201 method shows (N=30): [Ni-64] 8966 ± 11045 ppb, [Cu] 1244 ± 1636 ppb, [Fe] 426 ± 408 ppb, [Al] 1499 ± 2042 ppb, [Zn] 2717 ± 7196 ppb, [Co] 66 ± 84 ppb.

Conclusions: An automated method capable of producing high purity ⁶⁴Cu from ⁶⁴Ni targets has been developed. In summary, the entire process can be achieved in ~ 120 min (60 min for dissolution and resin loading, 30 min for resin elution and 30 min for evaporation of the 0.5 M acid)  min from EoB to EoS, with average yields of 2.54 ± 0.8 MBq/µAh/mg when irradiating with 35 μA for 2.5 to 3.5 h. The quality of the final product has been tested and it is suitable for all labelling processes.