Department of Oncology and Pathology, Karolinska Instituted, SE-171 77 Stockholm, Sweden.
Department of Radiopharmacy, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Biomolecules. 2021 Jul 29;11(8):1118. doi: 10.3390/biom11081118.
By using solid targets in medical cyclotrons, it is possible to produce large amounts of GaCl. Purification of Ga from metal ion impurities is a critical step, as these metals compete with Ga in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting GaClcould be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. GaCl was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The GaCleluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [Ga]Ga-DOTATOC and [Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.
通过在医用回旋加速器中使用固体靶，可以大量生产 GaCl。从金属离子杂质中纯化 Ga 是一个关键步骤，因为这些金属会与不同螯合剂与 Ga 的络合竞争，这会降低放射性标记产率。在这项工作中，我们通过在纯化过程中添加抗坏血酸，显著降低了铁（Fe）杂质的水平，所得的 GaCl 可用于临床相关 DOTA 基示踪剂的高产量放射性标记。GaCl 通过添加抗坏血酸的 UTEVA 树脂在洗涤溶液中进行回旋加速器生产和纯化。通过伽马光谱分析 Ga 洗脱液的放射性核纯度（RNP），通过 ICP-MS 分析金属含量，并通过与螯合剂 DOTA、NOTA 和 HBED 进行滴定。GaCl 洗脱液用于使用自动化合成模块对基于 DOTA 的示踪剂 DOTATOC 和 FAPI-46 进行 GMP 放射性标记。DOTA 螯合剂滴定给出了 491 ± 204 GBq/µmol 的表观摩尔活性（AMA）。GMP 合规的合成可产生高达 7 GBq/批次的[Ga]Ga-DOTATOC 和[Ga]Ga-FAPI-46（放射化学产率，RCY~60%，与发生器生产相比高十倍）。Ga 标记示踪剂的全面质量控制（QC）显示，放射性化学纯且至少在合成结束后四个小时内稳定的产品。
