Background Analytical data for ²²⁵Ac-labeled radiopharmaceuticals are currently obtained using thin-layer chromatography and high-performance liquid chromatography, the latter followed by offline fraction collection and delayed gamma-counting after secular equilibrium with gamma-emitting daughters has been reached. The procedures are slow and do not depict the distribution of daughter radionuclides. An inline HPLC detection setup is presented to enable faster and more informative analysis of a 225Ac-radiopharmaceutical. Results Four chromatographic signals were identified dorresponding to uncomplexed 221Fr with a most minor contribution of free 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 gamma-spectroscopy and beta liquid scintillation counting. The distribution of these species changed upon heating the reaction mixture or after addition of another ligand. Conclusion 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 alpha-emitting radionuclides. At the present stage, however, it should be regarded as a qualitative to semi-quantitative proof-of-principle.

GUILHEM Claude;  BALZER Matthias;  BRENNER Winfried;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  THONON David;  SPRECKELMEYER Sarah; 

2026-08-12

SPRINGER SCIENCE AND BUSINESS MEDIA DEUTSCHLAND GMBH

JRC146143

2365-421X (online),   

https://link.springer.com/article/10.1186/s41181-026-00476-6,    https://publications.jrc.ec.europa.eu/repository/handle/JRC146143,   

10.1186/s41181-026-00476-6 (online),