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Background <p>Analytical data for <sup>225</sup>Ac-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. These procedures are slow and do not depict the distribution of daughter radionuclides. An inline HPLC detection setup combining liquid scintillation detection and LaBr<sub>3</sub>-based gamma-spectroscopy is presented to enable faster and more informative analysis of a <sup>225</sup>Ac radiopharmaceutical.</p> Results <p>Four chromatographic signals were identified corresponding to uncomplexed <sup>221</sup>Fr with at most a minor contribution of free <sup>213</sup>Bi, [<sup>213</sup>Bi]Bi-PSMA I&amp;T, [<sup>225</sup>Ac]Ac-PSMA I&amp;T, and [<sup>209</sup>Pb]Pb-PSMA I&amp;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.</p> Conclusions <p>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 <sup>225</sup>Ac radiopharmaceuticals and other alpha-emitting radionuclides. At the present stage, however, it should be regarded as a qualitative to semi-quantitative proof-of-principle.</p>

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Inline gamma spectroscopy and liquid scintillation HPLC reveal daughters in 225Ac-radiopharmaceutical

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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  • Guilhem Claude,
  • Matthias Balzer,
  • Winfried Brenner,
  • Frank Bruchertseifer,
  • Alfred Morgenstern,
  • David Thonon,
  • Sarah Spreckelmeyer

摘要

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. 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 gamma-spectroscopy is presented to enable faster and more informative analysis of a 225Ac radiopharmaceutical.

Results

Four chromatographic signals were identified corresponding to uncomplexed 221Fr with at most a 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.

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 alpha-emitting radionuclides. At the present stage, however, it should be regarded as a qualitative to semi-quantitative proof-of-principle.