TY - JOUR
T1 - Cyclotron production of 68Ga in a liquid target
T2 - Effects of solution composition and irradiation parameters
AU - Pandey, Mukesh K.
AU - Byrne, John F.
AU - Schlasner, Katherine N.
AU - Schmit, Nicholas R.
AU - DeGrado, Timothy R.
N1 - Funding Information:
This project was financially supported by Department of Energy ( DE SC-0008947 ), USA, Mayo Clinic Department of Radiology and Mayo Clinic Center for Individualized Medicine.
Funding Information:
This project was financially supported by Department of Energy (DE SC-0008947), USA, Mayo Clinic Department of Radiology and Mayo Clinic Center for Individualized Medicine.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Cyclotron targetry
KW - Effect of solution composition
KW - Ga
KW - Solution target
UR - http://www.scopus.com/inward/record.url?scp=85065392886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065392886&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2019.03.002
DO - 10.1016/j.nucmedbio.2019.03.002
M3 - Article
C2 - 31085059
AN - SCOPUS:85065392886
SN - 0969-8051
VL - 74-75
SP - 49
EP - 55
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -