Unlocking the potential of scandium-44: reproducible production and radiolabelling methods towards clinical use in nuclear medicine

Abstract Purpose Scandium-44 is an emerging PET radionuclide with favourable physical properties, including a 4.04 h half-life and positron emission. These characteristics, combined with its coordination chemistry, similar to radiolanthanides, support its use in theragnostic radiopharmaceuticals. This study aims to optimize scandium-44 production and separation techniques to overcome existing challenges in product quality, namely its purity and pH reproducibility, enabling its use for automated radiopharmaceutical synthesis. Methods Radiochemical separation was evaluated using extraction and cation exchange resins (DGA, TK221, TK222, AG MP-50, AG 50 W-X8) through preliminary experiments. Scandium-44 was produced via proton irradiation of enriched calcium-44 targets and purified using an optimized chromatographic procedure based on DGA and AG MP-50 resins, yielding scandium-44 in ammonium acetate buffer. Radionuclidic and chemical purity were assessed by γ-ray spectrometry and ICP-MS, respectively. Radiolabelling performance was evaluated using DOTATOC, both manually and with an automated module system. Results Irradiation of the 20 mg targets for 1 h yielded up to 4.4 GBq of scandium-44 after separation. The optimized separation method provided reproducible product quality, with low metal contamination, radionuclidic purity exceeding 99% and a stable pH of 4. Radiolabelling of [ 44 Sc]Sc-DOTATOC achieved radiochemical purity > 95% at apparent molar activities up to 50 MBq/nmol. Automated synthesis on an E&Z module, produced [ 44 Sc]Sc-DOTATOC with 85% yield, suitable for multiple patient doses (180 MBq, 100 µg DOTATOC, 20 mL). Conclusions This study presents an optimized scandium-44 production and separation method, achieving high purity and activity concentration. Labelling to various ligands at high apparent molar activity indicates its purity, reproducibility and readiness for clinical translation.