Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers

By using solid targets in medical cyclotrons, it is possible to produce large amounts of (GaCl3)-Ga-68. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ 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 (GaCl3)-Ga-68 could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. (GaCl3)-Ga-68 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The Ga-68 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 (GaCl3)-Ga-68 eluate 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/p.mol. GMP-compliant syntheses yielded up to 7 GBq/batch [Ga-68]Ga-DOTATOC and [Ga-68]Ga-FAPI-46 (radiochemical yield, RCY similar to 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of Ga-68-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.