Demystifying solid targets: Simple and rapid distribution-scale production of [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 âž” 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 âž” 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.

Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets.

BACKGROUND: A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics, and generally lengthy separation chemistries for 64Cu/64Ni, upon which 61Cu chemistry is often based. METHODS: A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [61Cu]CuCl2, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. RESULTS: 61Cu saturation yields of 190 ± 33 MBq/µA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4% with an average radiochemical yield of 90.4 ± 3.2% (N = 5). The isolated activity was collected approximately 65 min post end of bombardment in ~ 2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10- 5% vs. 61Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 106, EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. CONCLUSION: High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.