Cyclotron production of ⁶⁸Ga in a liquid target: Effects of solution composition and irradiation parameters

To optimize ⁶⁸Ga production using a liquid cyclotron target, investigations were performed to compare production yields using different concentrations of [⁶⁸Zn]Zn(NO₃)₂, nitric acid, and irradiation parameters.

Different concentrations of [⁶⁸Zn]Zn(NO₃)₂ (0.6 M, 1.2 M and 1.42 M) in varying normality of nitric acid (0.8-1.5 N) were prepared and irradiated with protons (incident energy ~14 MeV) using a BMLT-2 liquid target at different beam currents (30-50 μA) and irradiation times (30-60 min). The ⁶⁸Ga production and saturation yields were calculated and compared. [⁶⁸Ga]GaCl₃ was isolated using in-house developed hydroxamate resin and optimized for routine application. Recycling of [⁶⁸Zn]Zn(NO₃)₂ from the recovered target solution was also investigated.

On increasing concentration of [⁶⁸Zn]Zn(NO₃)₂ from 0.6 M to 1.2 M in 0.8 N nitric acid, decay corrected yield of ⁶⁸Ga at EOB was found to be 1.64 GBq (44.4 mCi) and 3.37 GBq (91.0 mCi), respectively at 30 μA beam current, indicating production yield was proportional to zinc nitrate concentration for a 30 min irradiation. However, when beam current was increased to 40 μA while maintaining nitric acid concentration at 0.8 N, the proportional relationship of ⁶⁸Zn-concentration with ⁶⁸Ga production yield was lost [0.6 M, 2.29 GBq (61.9 mCi); 1.2 M, 3.6 GBq (97.3 mCi)] for a 30 min irradiation. In fact, the effect was more profound for 60 min irradiations [0.6 M, 2.96 GBq (80.0 mCi); 1.2 M, 4.25 GBq (115 mCi)]. Increasing nitric acid concentration to 1.25-1.5 N improved ⁶⁸Ga production yield for 40 μA, 60-min irradiations (1.2 M; 5.17 GBq (140 mCi)). MP-AES analysis showed metal impurities as <0.20 μg Ga (n = 3), <0.93 μg Zn (n = 3) and < 2.7 μg Fe (n = 3). Based on above finding, 1.42 M [⁶⁸Zn]Zn(NO₃)₂ in 1.2 N-HNO₃ solutions were also studied to achieve highest production yields of 9.85 ± 2.09 GBq (266 ± 57 mCi) for 60 min irradiation at 40 μA beam current. After recycling,> 99% pure recycled [⁶⁸Zn]zinc nitrate was obtained in 82.6 ± 13.6% yield.

⁶⁸Ga production yields were dependent on all four variables: concentrations of [⁶⁸Zn]Zn(NO₃)₂ and nitric acid, beam current and duration of irradiation. Of note, increasing beam current and irradiation time may require increased concentrations of nitric acid to achieve expected increments in ⁶⁸Ga production yield.