The 68Ge/68Ga generator for enhancing productivity and reducing costs in nuclear medicine: experience from a university hospital

Abstract

Background

Sustainability in healthcare, particularly Nuclear Medicine, is essential, especially in managing radioactive materials. Traditional centralized production of Fluorine-18 tracers for PET imaging faces challenges like transport logistics, decay losses and supply chain vulnerabilities. Decentralized production with radionuclide generators, such as the Germanium-68/Gallium-68 (⁶⁸Ge/⁶⁸Ga) generator, offers on-demand isotope production, improving accessibility and precision imaging. This study evaluates the long-term performance (8 years) of ⁶⁸Ga-based radiopharmaceutical production in a Nuclear Medicine Division, focusing on efficiency, sustainability, and cost.

Results

Between 2016 and 2024, 416 batches of ⁶⁸GaCl₃ and 2455 batches of ⁶⁸Ga-based radiopharmaceuticals were produced. Data from systematic quality controls on generator eluates and tracers, such as ⁶⁸Ga-PSMA (1800 batches) and ⁶⁸Ga-DOTATOC (610 batches), were evaluated. All ⁶⁸GaCl₃ eluates met Ph. Eur. specifications, with negligible ⁶⁸Ge breakthrough (mean 0.0000068%) and consistently high radiochemical purity (100%). Radiopharmaceuticals showed stable quality over time, with > 98% purity for ⁶⁸Ga-DOTATOC and > 99% for ⁶⁸Ga-PSMA. Generators performance remained reliable, with an average elution yield of 74.8% (range 63.4–84.7%) and up to 466 elutions/year reached in 2024 without quality degradation. The correlation between estimated and measured end-of-synthesis activities was strong (R² ≈ 1), supporting accurate production planning. Clinical PET scans increased over sixfold, from 144 in 2016 to 920 in 2025. The high-sensitivity PET/CT system helped reduce injected activity and acquisition time, improving throughput and sustaining growth. The clinical-to-production ratio progressively decreased from 1 (1 batch/exam) to 0.42 for ⁶⁸Ga-PSMA (range 0.37–0.51) and 0.49 for ⁶⁸Ga-DOTATOC (range 0.40–0.60), indicating better batch utilization and workflow efficiency. Cost analysis showed module-based synthesis was most efficient during high-yield phases of the generators, while kit-based approaches were more cost-effective at later stages. Supply logistics of precursors and reagents has shown to be more sustainable for in-house production of radiopharmaceuticals compared to the purchased ones from external facilities.

Conclusions

The ⁶⁸Ge/⁶⁸Ga generator supports reliable, sustainable, and cost-effective radiopharmaceutical production, enhancing efficiency and clinical capacity in PET imaging.