Demystifying solid targets: Simple and rapid distribution-scale production of [68Ga]GaCl3 and [68Ga]Ga-PSMA-11

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.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]).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.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.