A System for Localizing Alpha-Emitting Radionuclide at the Subcellular Scale: A Feasibility Study
Abstract
Purpose
This study aims to demonstrate the feasibility of a multifocal radioluminescence microscopy (RLM) framework to localize alpha-emitting radionuclide positions at the subcellular level.
Methods
Radioluminescence interactions between alpha particles and a GAGG:Ce scintillator were modeled using OpenTOPAS Monte Carlo simulation. Detected photons were filtered by numerical aperture (NA=1.4) and quantum efficiency, then back-projected to two focal planes (98 and 99 um depth) using ray-tracing. A reconstruction pipeline 1) extracted track centroids in each focal plane, 2) matched corresponding tracks between planes, and 3) extrapolated the inferred trajectories back to their emission points. Performance was evaluated using detection rate and localization error across monoenergetic alpha energies (4-8 MeV) and 225Ac decay chain conditions. Detection rate was defined as the ratio of reconstructed decay origins to the total number of decay events simulated within the field of view, and localization error was defined as the Euclidean distance in the x–y plane between the reconstructed origin and the corresponding ground-truth decay position.
Results
For monoenergetic alpha sources, increasing the energy from 4 MeV to 8 MeV improved the detection rate (78% to 94%) and spatial resolution (2.2 to 1.9 µm), reflecting the advantages of reduced scattering at higher energies. The framework also maintained a median localization error of 1-1.5 µm, confirming its precision for subcellular-level detection. For uniformly distributed 225Ac sources of 1 kBq, detection rate was 32% with median localization error of 1.1 µm. The observed localization trends suggest micrometer-scale origin estimation (median errors of 1-2 µm) at activities up to 0.2 kBq per cell, supporting the practical potential for activity ranges relevant to targeted alpha therapy.
Conclusion
This study demonstrated the physical foundation of a reconstruction pipeline for localizing alpha-emitting radionuclides using multifocal RLM.