If 3–4 patient doses per batch are typically obtained when the generator is new, only 1–2 doses per batch are produced toward the end of its use. Additionally, decay of the parent 68Ge leads to elution of less and less 68Ga radioactivity over the generator lifespan. This means the generator may be used for radiolabeling 2–3 times a day during normal working hours. After elution, several hours are needed for 68Ga ingrowth before satisfactory radioactivity levels can be eluted again. The small amount of radioactivity that can be eluted (e.g., ~1.5 GBq from a new generator) requires multiple generators to scale up radiopharmaceutical production. The 68Ge/ 68Ga-generators are easy to use but do suffer from several drawbacks. This relatively short half-life is suitable for positron emission tomography (PET) diagnostics when radiolabeling small molecules with fast pharmacokinetics. Gallium-68 ( 68Ga) is a positron-emitting radioisotope with a half-life of 68 min. Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis. GMP-compliant syntheses yielded up to 7 GBq/batch Ga-DOTATOC and Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. The 68GaCl 3 eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. The 68Ga 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. 68GaCl 3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl 3 could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. Purification of Ga 3+ from metal ion impurities is a critical step, as these metals compete with Ga 3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl 3.
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