Scalable 68Ga Cold Kit Radiolabeling: High-Throughput Preparation of [68Ga]Ga-Edotreotide via Aliquoting and Dual Generator Strategy

Abstract The aim of the study was to develop and assess alternative radiolabeling strategies for SOMAKIT-TOC using gallium-68, with the aim of improving cost-efficiency by increasing the number of examinations per cold kit while maintaining radiochemical quality suitable for clinical use. Four protocols were evaluated using triplicate test radiolabelings: (1) the reference method using a single generator and a full kit; (2) dual-generator elution into a full kit; (3) single-generator elution into two sequentially radiolabeled aliquots from one kit; and (4) dual-generator elution into two sequentially radiolabeled aliquots from one kit. Radiochemical purity (RCP) was assessed by radio-thin layer chromatography (rTLC) and radio-high performance liquid chromatography (rHPLC), and radiochemical stability was monitored over 4 hours. Additional quality controls parameters included pH, sterility, and peptide integrity in aliquot solution. Procedures 1 and 3 were further assessed in clinical routine. All protocols yielded radiopharmaceuticals with mean RCP values above 95% by rTLC. Procedure 2 significantly increased the final activity compared with Procedure 1. Procedure 3 enabled doubling the number of examinations per kit while maintaining RCP comparable to the reference method Procedure 4 showed greater variability. Radiolabeled products remained stable over 4 hours as assessed by rTLC, although rHPLC revealed a gradual decrease in purity. In clinical use, Procedure 3 allowed 94 preparations that met diagnostic needs, though 33% had RCP between 80 and 95%. Aliquoting a single cold kit for dual radiolabeling using one generator is feasible and cost-effective, although it is associated with greater RCP variability. Dual-generator strategies yield higher activity but may further compromise RCP. Further optimization is required to improve robustness of off-label protocols while preserving the highest product quality.