Johan Svedjehed1, Martin Pärnaste1, Katherine Gagnon2. 1. Cyclotrons and TRACERcenter, GEMS PET Systems AB, GE Healthcare, Uppsala, Sweden. 2. Cyclotrons and TRACERcenter, GEMS PET Systems AB, GE Healthcare, Uppsala, Sweden. Electronic address: katherine.gagnon@ge.com.
Abstract
BACKGROUND: As the demand for 68Ga continues to grow, there is increasing interest in single-to-multi-Curie production quantities of both [68Ga]GaCl3 and tracers such as [68Ga]Ga-PSMA-11. While such quantities are possible with solid targets, this implementation is often challenging as it typically requires significant site expertise for solid target processing and careful operator-dependent synchronization of multiple independent time-sensitive chemistry steps. Herein we focus on a fully automated solid target production and purification process whereby we avoid the need for tongs/tele-pliers, and have simplified the chemistry by implementing a single sequence (i.e. "time-list") to execute cassette-based dissolution, purification, and labeling. METHODS: Electroplated 68Zn was irradiated in a PETtrace prototype automated solid target system. Following irradiation, and using a single FASTlab time-list, the 68Zn was automatically dissolved with HCl/H2O2 and purified as [68Ga]GaCl3 using a combination of resins (ZR/TK400, A8, TK200: Triskem). For select experiments, [68Ga]Ga-PSMA-11 was also produced on the same cassette/single time-list (N = 4), or, by kit labeling (N = 1). Efforts focused towards on-cassette production of [68Ga]GaCl3 strived to maximize activity and quality, whereas efforts focused towards on-cassette production of [68Ga]Ga-PSMA-11 aimed at limiting the entire production cycle to 1 h including the irradiation time (i.e. start-of-bombardment ➔ end-of-synthesis [EOS]). RESULTS: For the high activity triplicate [68Ga]GaCl3 productions (i.e. 80 μA, 102 min, 216 ± 10 mg), [68Ga]GaCl3 was purified (end-of-bombardment ➔ end-of-purification [EOP]) in ~28 min with activity yields of 181 ± 8 GBq at EOP and average radiochemical yields of 66 ± 5%. Average AMAs of 2.26 ± 0.16 TBq/μmol using DOTA (N = 3) and 12.00 TBq/μmol using HBED (PSMA-11) (N = 1) at EOP were measured. For the single kit test, (80 μA, 120 min, 263 mg 68Zn) for which 18 mg ascorbic acid was added to the buffer, 199 GBq of [68Ga]Ga-PSMA-11 was successfully produced (thin layer chromatography-based radiochemical purity >99% at 6 h EOS). Finally, for efforts focused at expedient [68Ga]Ga-PSMA-11, up to 42 GBq [68Ga]Ga-PSMA-11 with a radiochemical yield of 51.2% was produced in 63 min, including beamtime, using 220 mg of 68Zn as target material. CONCLUSION: With the goal of simplifying solid target production and purification efforts, automated methods using single-use, cassette-based approaches for rapid, large-scale, single time-list production of [68Ga]GaCl3 and [68Ga]Ga-PSMA-11 were developed. These methods were simple to execute and yielded high quality multi-Curie levels of both [68Ga]GaCl3 and [68Ga]Ga-PSMA-11.
BACKGROUND: As the demand for 68Ga continues to grow, there is increasing interest in single-to-multi-Curie production quantities of both [68Ga]GaCl3 and tracers such as [68Ga]Ga-PSMA-11. While such quantities are possible with solid targets, this implementation is often challenging as it typically requires significant site expertise for solid target processing and careful operator-dependent synchronization of multiple independent time-sensitive chemistry steps. Herein we focus on a fully automated solid target production and purification process whereby we avoid the need for tongs/tele-pliers, and have simplified the chemistry by implementing a single sequence (i.e. "time-list") to execute cassette-based dissolution, purification, and labeling. METHODS: Electroplated 68Zn was irradiated in a PETtrace prototype automated solid target system. Following irradiation, and using a single FASTlab time-list, the 68Zn was automatically dissolved with HCl/H2O2 and purified as [68Ga]GaCl3 using a combination of resins (ZR/TK400, A8, TK200: Triskem). For select experiments, [68Ga]Ga-PSMA-11 was also produced on the same cassette/single time-list (N = 4), or, by kit labeling (N = 1). Efforts focused towards on-cassette production of [68Ga]GaCl3 strived to maximize activity and quality, whereas efforts focused towards on-cassette production of [68Ga]Ga-PSMA-11 aimed at limiting the entire production cycle to 1 h including the irradiation time (i.e. start-of-bombardment ➔ end-of-synthesis [EOS]). RESULTS: For the high activity triplicate [68Ga]GaCl3 productions (i.e. 80 μA, 102 min, 216 ± 10 mg), [68Ga]GaCl3 was purified (end-of-bombardment ➔ end-of-purification [EOP]) in ~28 min with activity yields of 181 ± 8 GBq at EOP and average radiochemical yields of 66 ± 5%. Average AMAs of 2.26 ± 0.16 TBq/μmol using DOTA (N = 3) and 12.00 TBq/μmol using HBED (PSMA-11) (N = 1) at EOP were measured. For the single kit test, (80 μA, 120 min, 263 mg 68Zn) for which 18 mg ascorbic acid was added to the buffer, 199 GBq of [68Ga]Ga-PSMA-11 was successfully produced (thin layer chromatography-based radiochemical purity >99% at 6 h EOS). Finally, for efforts focused at expedient [68Ga]Ga-PSMA-11, up to 42 GBq [68Ga]Ga-PSMA-11 with a radiochemical yield of 51.2% was produced in 63 min, including beamtime, using 220 mg of 68Zn as target material. CONCLUSION: With the goal of simplifying solid target production and purification efforts, automated methods using single-use, cassette-based approaches for rapid, large-scale, single time-list production of [68Ga]GaCl3 and [68Ga]Ga-PSMA-11 were developed. These methods were simple to execute and yielded high quality multi-Curie levels of both [68Ga]GaCl3 and [68Ga]Ga-PSMA-11.
Authors: Sashi Debnath; Ning Zhou; Mark McLaughlin; Samuel Rice; Anil K Pillai; Guiyang Hao; Xiankai Sun Journal: Int J Mol Sci Date: 2022-01-21 Impact factor: 5.923