Parameterizable salivary gland model for small-scale Monte Carlo radiopharmaceutical therapy dosimetry: evaluation of...

Standard of care radiopharmaceutical therapy (RPT) may result in dose-limiting side effects of the salivary glands including sialadenitis and xerostomia that are inconsistent with outcomes from external beam for equivalent absorbed doses (ADs). This work develops a parameterizable 'Macro-to-Micro' (M2μ) model that demonstrates the consideration of small-scale dosimetry in comparison to conventional methods that typically assume uniform voxel or organ-level uptake. Anatomical features of the salivary gland are represented by annular structures (a centralized branching network of ducts, including excretory, lobar, interlobular) and small-scale voxels (intralobular ducts and acinar cells) with dimensions set to reproduceex vivomurine histopathology measurements and scaled up in size for extrapolation to humans. Simulations were performed by scoring and recordingS-value histograms to the target ductal and acinar cells, for two beta emitters (¹⁷⁷Lu,¹³¹I) and one alpha emitter (²²⁵Ac). Four idealized activity distributions were created to assign activity to surfaces and volumes of the annuli, and GEANT4 v11 was used for radiation transport calculations. Comparisons against whole gland uniform spherical self-doseS-value calculations were conducted to validate the radiation transport and to highlight differences between M2μand conventional dosimetry approaches. Analyses for both models showed greaterS-value variation in comparison to the homogeneously distributed activityS-value calculation. The most notable result was that the calculatedS-values differed between different branches, depending on the geometric size of the annuli. For the surrounding acinar cells,S-values from ductal cells decreased as a function of distance from the branching structures. High variability ofS-values, depending on ductal cell dimensions as well as within the acinar cell distribution of the salivary gland highlights the potential clinical utility of small-scale approaches to RPT salivary gland dosimetry, contingent on clinical translation and validation. To this end, future work should further refine the model and incorporate small-scale activity distributions from pre-clinical and translational studies.