Development of Zinc Targetry: Production of diagnostic 67Ga and theranostic 67Cu

Objectives: Radionuclide availability plays a key role for development of new radiopharmaceuticals. Moreover, theranostic matched pairs of radionuclides have aroused interest in the last couple of years. On the one hand, 68Ga has been used as a diagnostic counterpart to the therapeutic β--emitter 177Lu, however, due to its short half-life (68 min), further alternatives have to be considered. In particular 67Ga (half-life: 3.26 d) as the longest-lived of the radiogallium isotopes has γ-lines that can be used for SPECT imaging (93.3 keV, 184 keV). On the other hand, 67Cu is referred as a theranostic radionuclide due to its β--emission and γ-emission suitable for SPECT, forming a perfect matched pair with the PET radionuclides 61/64Cu. At HZDR the zinc targetry and target chemistry developed for 67Cu production [1] has been applied to produce 67Ga.

Methods: 67Cu production consisted of proton irradiation (16.8 MeV, 60 µA, up to 20 h, 30° solid target configuration) of 70Zn targets (100-140 mg/cm2) electrodeposited onto silver via the 70Zn(p,α)67Cu nuclear reaction. Target work-up comprise a two- or three-step chromatographic column separation [1]. Gamma spectroscopy was used to quantify the radionuclidic purity (RNP), ICP-MS for the molar activity (Am) and test radiolabeling with the macrocyclic complexing agent TETA for apparent molar activity (AMA) quantification. Additionally, 67Ga was produced by proton irradiation (19 MeV, 35 µA, 2 h, 30° solid target configuration) of enriched 68Zn targets (60-70 mg/cm2) electrodeposited onto gold via the 68Zn(p,2n)67Ga nuclear reaction. After “cooling down” of the target (12-16 h, decay of co-produced 68Ga), the radiochemical separation consisted of a two-step chromatographic column separation; first a 1 mL TK400 cartridge followed by a 0.3 mL DGA branched cartridge. RNP was quantified by gamma spectroscopy.

Results: Activity yields of > 1.0 GBq 67Cu at EOB were reached, leading to over 800 MBq [67Cu]CuCl2 at EOP in 1.5 mL of 0.05 M HCl with RNP g.t. 99.5 % (at EOP) and AMA up to 300 GBq/µmol (EOB corrected). Furthermore, activities of up to 1.8 GBq 67Ga at EOB, and ca. 1.0 GBq [67Ga]GaCl3 at EOP in 0.5 mL of 0.05 M HCl were produced. First 67Ga gamma spectroscopy results showed a RNP of over 99 % at EOP. In both cases, the activity reached represented about 60 % to 70 % of the calculated yield.

Conclusions: Production of the radionuclides 67Cu and 67Ga from proton irradiation of zinc targets is being performed at HZDR. Both radionuclide product solutions proved sufficient quality regarding RNP and radiolabeling properties. further optimization of the 67Ga production is planned. Although 67Cu activities produced are not enough for clinical demand, the obtained yields are adequate for first in vitro and in vivo studies while other production routes are being explored.

References:

[1] Brühlmann SA, Walther M, Kreller M, Reissig F, Pietzsch H-J, Knieß T and Kopka K. Pharmaceuticals 2023, 16, 314.