Experimental determination and Monte Carlo validation of ²²⁵ Ac absorbed dose

Radiopharmaceutical therapy (RPT) with alpha-emitting radionuclides, such as 225 Ac, offers highly localized dose delivery due to its short particle range and high linear energy transfer. However, the complex decay chains of most clinically relevant, alpha-emitting radionuclides, such as 225 Ac, introduce challenges in dosimetry. To address these challenges, this study presents the first direct comparison of experimentally measured absorbed dose to air for 225 Ac with a commonly used Monte Carlo (MC) platform, Tool for Particle Simulation (TOPAS) and a research activity-to-absorbed-dose calculation platform. The spatial distribution of the deposited 225 Ac source was determined with digital autoradiography, activity was determined with a gamma spectrometer, and self attenuation was quantified with an alpha spectrometer. Absorbed dose to air was measured using an extrapolation chamber. MC correction factors were applied to bridge experimental measurements and voxelized dose calculations. The radiopharmaceutical assessment platform for internal dosimetry (RAPID), a Geant4-based dose calculation platform, was used with digital autoradiography-derived images to compute absorbed dose distributions. Experimental and simulated absorbed dose values were in strong agreement, with experimental measurements consistently 1%–2% higher than TOPAS predictions across all air gaps. RAPID simulations, despite using voxelized source distributions derived from the digital autoradiography imaging, consistently measured lower absorbed doses than both experimental and TOPAS results. The digital autoradiography system enabled high-resolution activity mapping for source characterization, reducing uncertainties in MC and RAPID modeling. This work provides the first validation of a RPT activity-to-absorbed-dose calculation platform against absolute measurements, demonstrating a robust framework for integrating experimental and computational dosimetry. The methodology achieved a measured absorbed dose uncertainty of 3.00% ( k = 1), consistent with the general magnitude reported in previous work, despite optimizations made to the extrapolation chamber. This suggests that while improvements were effective, the inherent complexities of 225 Ac, such as its long decay chain, progeny migration, and diverse emission energies, pose additional challenges to achieving further reductions in uncertainty. These findings lay the foundation for future studies involving other radionuclides, advancing traceability for the complete RPT dosimetry workflow.