Inline Gamma Spectroscopy and Liquid Scintillation HPLC Reveal Daughters in 225Ac-Radiopharmaceutical

Background Analytical data for ²²⁵Ac-labeled radiopharmaceuticals are currently obtained using thin-layer chromatography or high-performance liquid chromatography followed by offline fraction collection and delayed γ-counting after secular equilibrium with γ-emitting daughters has been reached. These procedures are slow and do not depict the distribution of daughter radionuclides. An inline HPLC detection setup combining liquid scintillation detection and LaBr₃-based γ-spectroscopy is presented to enable faster analysis and to establish reproducible quality control parameters for ²²⁵Ac radiopharmaceuticals. Results Four chromatographic signals were identified corresponding to uncomplexed ²²¹Fr and ²¹³Bi, [²¹³Bi]Bi-PSMA I&T, [²²⁵Ac]Ac-PSMA I&T, and [²⁰⁹Pb]Pb-PSMA I&T. The retention times corresponded to those of the non-radioactive analogs determined by UV detection. Assignments were confirmed by fraction collection followed by γ-spectroscopy and β liquid scintillation counting. Conclusions The combined detection setup enables rapid observation of isotope distribution and daughter behavior during chromatographic analysis and avoids fraction handling by operating as a closed system, thereby reducing contamination risk and radiation exposure. This approach may contribute to improved quality control procedures for ²²⁵Ac radiopharmaceuticals and other α-emitting radionuclides.