Rodnick Melissa E, Sollert Carina, Stark Daniela, Clark Mara, Katsifis Andrew, Hockley Brian G, Parr D Christian, Frigell Jens, Henderson Bradford D, Abghari-Gerst Monica, Piert Morand R, Fulham Michael J, Eberl Stefan, Gagnon Katherine, Scott Peter J H
Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
GE Healthcare, GEMS PET Systems, Uppsala, Sweden.
EJNMMI Radiopharm Chem. 2020 Nov 12;5(1):25. doi: 10.1186/s41181-020-00106-9.
To optimize the direct production of Ga on a cyclotron, via the Zn(p,n)Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced Ga, extraction of [Ga]GaCl and subsequent [Ga]Ga-PSMA-11 labeling using an automated synthesis module.
Irradiations of a 1.0 M solution of [Zn]Zn(NO) in dilute (0.2-0.3 M) HNO were conducted using GE PETtrace cyclotrons and GE Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of Ga through the Zn(p,2n)Ga reaction without unduly compromising Ga yields. We also evaluated the effects of varying beam times (50-75 min) and beam currents (27-40 μA). Crude Ga production was measured. The extraction of [Ga]GaCl was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [Ga]GaCl was used to label [Ga]Ga-PSMA-11 that was intended for clinical use.
The decay corrected yield of Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [Zn]Zn(NO) at 0.3 M HNO Target/chemistry performance was more consistent when compared with 0.2 M HNO. Radionuclidic purity of Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined Ga) for a practical clinical product shelf-life. The activity yield of [Ga]GaCl was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA).
Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [Ga]Ga-PSMA-11 and is a viable alternative to traditional Ge/Ga generators.
通过使用液体回旋加速器靶材的Zn(p,n)Ga反应，优化回旋加速器上Ga的直接生产。我们研究了回旋加速器生产的Ga的产率、[Ga]GaCl的提取以及随后使用自动合成模块进行的[Ga]Ga-PSMA-11标记。
使用GE PETtrace回旋加速器和GE Ga液体靶材，对稀释（0.2 - 0.3 M）HNO₃中的1.0 M [Zn]Zn(NO₃)₂溶液进行辐照。质子束能量降低至标称的14.3 MeV，以尽量减少通过Zn(p,2n)Ga反应共产生Ga，同时又不过度影响Ga的产率。我们还评估了不同束流时间（50 - 75分钟）和束流电流（27 - 40 μA）的影响。测量了粗Ga的产量。在GE FASTlab Developer平台上使用双柱固相法进行[Ga]GaCl的提取。提取的[Ga]GaCl用于标记供临床使用的[Ga]Ga-PSMA-11。
对于60分钟的束流，EOB时Ga的衰变校正产率通常> 3.7 GBq（100 mCi），在0.3 M HNO₃中辐照[Zn]Zn(NO₃)₂。与0.2 M HNO₃相比，靶材/化学性能更一致。EOB时Ga的放射性核素纯度通常> 99.8%，满足欧洲药典规定的实用临床产品保质期要求（总Ga< 2%）。[Ga]GaCl的活度产率通常> 50%（~ 1.85 GBq，50 mCi）；随着工艺优化，产率提高。EOS时[Ga]Ga-PSMA-11的标记产率接近定量（~ 1.67 GBq，45 mCi）。回旋加速器生产的[Ga]Ga-PSMA-11经过全面的质量控制、稳定性和无菌测试，并作为研究性新药通过美国食品药品监督管理局在密歇根大学以及皇家阿尔弗雷德王子医院（RPA）供人体使用。
对液体靶材进行回旋加速器直接辐照可提供临床相关量的[Ga]Ga-PSMA-11，是传统Ge/Ga发生器的可行替代方案。
