Optimization of [68Ga] Production via Cyclotron Irradiation 1.0 M Zn(NO3)2 solution for the Synthesis of [Ga-68] PSMA-11 HBED.

465 Objectives: To elucidate the optimal cyclotron conditions for production of consistently high yields of [68Ga], using 1.0 M [68Zn] Zn(NO3)2 in 0.2 M HNO3 target solution, as well as testing FASTlab synthesis of [68Ga] Ga-PSMA-11-HBED using cyclotron produced [68Ga]. Methods: A GE Healthcare PETtrace cyclotron and liquid targetry was used for [68Ga] production. The liquid target comprises a 2.3 mL niobium target insert, a 200 µm aluminum beam energy degrader foil, and a 25 µm niobium foil in contact with a 25 µm havar foil. Initial experiments resulted in standard irradiation conditions of 60 minutes run time at 38 µA beam current. Target cleaning, required a 15 to 30 minute irradiation of 0.6 M HNO3 solution performed between [68Ga] production runs. A dedicated surveillance run was deemed necessary to ensure reliable target performance. At the end of bombardment, [68Ga] was delivered to a FASTlab synthesizer for [68Ga] purification and then synthesis of [68Ga]Ga-PSMA-11 HBED. The latter was completed using FASTlab Developer software. A single FASTlab cassette was used for isotope purification and drug synthesis. It was constructed from FASTlab Developer kit components according to directions supplied by GE Healthcare. Results: Irradiation times were not extended beyond 60 minutes. Data indicates that target pressures > 130 psi were indicative of a less reactive isotope leading to lower radiochemical yields of [68Ga] PSMA-11 HBED. Optimal beam current was determined to be in the range of 35 to 38 µA. Using standard irradiation conditions of 38 µA and 60 minutes, unpurified target yields averaged 122.4 mCi at EOB (n=6). Purified [68Ga] yields were 81.4 mCi at EOS (n=6). Higher beam currents results in increased co-production of [67Ga]. Impossible to remove, this isotope has a long half-life of 78.26 hours. Performance of the target is reliant on systematic cleaning between [68Ga] irradiations due in part to Zn(OH)2 accumulation. Formation of hydrogen and oxygen gas via radiolysis of water probably leads to a corresponding rise in target pressure [1]. Our data suggests that target life is 500 to 700 µAhours. Maintenance of reliable isotope production may require surveillance of target performance. We suggest that target rebuilds are necessary if the unpurified [68Ga] target yield is 130 psi. Under these conditions and controls, FASTlab production of [68Ga] Ga PSMA-11 HBED proved to be reliable and reproducible, average radiochemical yield of 45.9 mCi at EOS (n=7). Typicallyradiochemical yields deteriorate with increased uAhours. Radiochemical yields between 40 to 50 mCi at EOS were routinely achievable, with radiochemical purity > 95%. Preliminary experiments suggest that a small increase in target output may be achieved with increased concentrations of [68Zn] Zn(NO3)2. A selection of different concentrations were tested (Figure 1). A 1.2 M solution of [68Zn] Zn(NO3)2 in 0.3 M HNO3 resulted in an unpurified [68Ga] yield of 141 mCi. This is approximately a 5-10 % increase in the quantity of unpurified isotope when compared with standard run conditions. Along with this increase is a tandem increase in target pressure. (Figure 1). Conclusions: Production of [68Ga] via cyclotron irradiation of a commercially available liquid target is achievable, provided the target is properly maintained. Main limitations are i) quantity of [68Ga] production and ii) target life between rebuilds. The cyclotron produced [68Ga] can then be successfully used to reliably produce [68Ga] PSMA-11 HBED on a FASTlab synthesizer platform, with reproducible yields. References: [1] Pandey MK, Engelbrecht HP, Byrne JP, Packard AB, DeGrado TR. Production of 89Zr via the 89Y(p,n)89Zr reaction in aqueous solution: effect of solution composition on in-target chemistry. Nuc Med Biol 2014;4(4):309-16