Abstract
69
Objectives: 68Ge/68Ga generator-based clinical production of [68Ga]Ga-PSMA-11 began at the University of Michigan in February 2018. Due to ongoing uncertainty in generator costs, delivery timelines, and increasing patient demand, we validated and implemented clinical production of [68Ga]Ga-PSMA-11 using cyclotron-produced 68Ga from a liquid target, in early February 2019, with routine production of 1.4-1.8 GBq (40-50 mCi) final product demonstrated [1]. In an effort to meet our steady patient demand, we increased our synthetic yields while maintaining liquid target infrastructure by implementing simultaneous production of 68Ga in two liquid targets via dual beam irradiation. Following bombardments, the contents of both targets were combined and used for the production of [68Ga]Ga-PSMA-11.
Methods: 68Ga was produced by proton irradiation of 1.0 M [68Zn]Zn(NO3)2 in dilute (i.e. 0.3 M) HNO3 on a GE PETtrace cyclotron similar to our previous report [1]. The main difference to our previous efforts included the use of dual target irradiation, and furthermore, following preliminary tests [2] a minor change from 25μm each Havar and niobium foils to 50 μm titanium in the targets. The targets were irradiated at 35-40 μA (ports 3 and 6) for ~60 min at a nominal proton energy of 14.6 MeV. The irradiated target solutions were sequentially delivered to a single external vial within the hot cell, with beam maintained on the second target while the first was being emptied. This vial was pre-loaded with 5.5 mL of metal free H2O to ensure the HNO3 concentration was ≤0.1 M prior to column loading and had been connected to a FASTlab synthesis module before receipt of the radioactivity. The resulting solution was processed for single cassette production of [68Ga]Ga-PSMA-11 (n = 7) with full quality control analyses performed to ensure clinical integrity.
Results: The total time from EOB (counting from EOB of the 1st target) to EOS was 45 min following slight adjustments to delivery and column loading times, as compared to 40 min from EOB to EOS for single [68Ga]Ga-PSMA-11 runs [1]. Yields were, 3.7 ± 0.2 GBq (100 ± 6 mCi) at EOS (n = 7). The final product consistently met quality control criteria previously established in our [68Ga]Ga-PSMA-11 IND application approved by the US FDA and 4 batches have been used clinically.
Conclusions: Following optimization on the target setup, dilution of the irradiated solutions, and column loading, successful combination of two simultaneously irradiated 68Ga liquid targets to produce high quality [68Ga]Ga-PSMA-11 has been demonstrated, with >3.7 GBq (>100 mCi) isolated for clinical use. Further optimization efforts are underway with a goal of producing >4.4 GBq (>120 mCi) of [68Ga]Ga-PSMA-11 from a single production run. Acknowledgements: We thank Mara Clark (UM) for assistance with chemistry and and Steve Grosch (GE) for help with targetry. References: [1] Rodnick et al., EJNMMI Radiopharm. Chem. (2020) 5:Article 25.[2] Gagnon et al., Eur J Nucl Med Mol Imaging (2020) 47 (Suppl 1): S1-S753