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Updated: Jun 7, 2026

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Framework for subcellular localization of alpha-emitting radionuclides.

Seohan Kim1,2,3, Wonmo Sung1,2,3

  • 1Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Physics in Medicine and Biology
|June 5, 2026
PubMed
Summary

This study introduces multifocal radioluminescence microscopy (RLM) for precise alpha-emitting radionuclide localization. The new method achieves high detection rates and micrometer-scale resolution, crucial for targeted alpha therapy research.

Keywords:
Monte Carlo simulationalpha particle imagingradioluminescence microscopytargeted alpha therapy

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Area of Science:

  • Nuclear medicine and imaging
  • Medical physics
  • Radiochemistry

Background:

  • Accurate cellular and subcellular radionuclide distribution assessment is vital for targeted alpha therapy (TAT) due to alpha particles' short range.
  • Conventional single-focal plane radioluminescence microscopy (RLM) lacks depth information, hindering reliable localization of alpha decay origins.
  • Existing methods struggle with oblique trajectories and depth ambiguity, limiting quantitative dosimetry at the cellular scale.

Purpose of the Study:

  • To develop and validate a multifocal RLM framework for quantitative localization of alpha-emitting radionuclides.
  • To enable accurate micrometer-scale dosimetry essential for advancing targeted alpha therapy.
  • To overcome the limitations of single-focal plane RLM in determining decay origins.

Main Methods:

  • Modeled a multifocal RLM system using Monte Carlo simulations (OpenTOPAS) including alpha transport and photon detection.
  • Generated simultaneous RLM images at two focal planes within a GAGG:Ce scintillator.
  • Developed a reconstruction pipeline to localize decay origins by matching tracks across focal planes and extrapolating trajectories.

Main Results:

  • Achieved >85% detection rates for alpha energies relevant to 225Ac daughters, with ~2 µm spatial resolution for monoenergetic sources.
  • Demonstrated median lateral localization errors of 1-2 µm for 225Ac decay chains at TAT-relevant activity levels (0.2-0.4 kBq/cell).
  • Provided quantitative insights into trade-offs between detection efficiency, source density, and particle energy for experimental design.

Conclusions:

  • Multifocal RLM is a feasible quantitative framework for micrometer-scale alpha-emitting radionuclide localization.
  • The approach extends RLM from qualitative visualization to quantitative decay origin estimation.
  • Establishes a foundation for experimental validation of subcellular radionuclide distributions in TAT research.