2001 - Evaluation of Salivary Gland Mouse and Human Model for Small-Scale Monte Carlo Radiopharmaceutical Therapy Dosimetry

02:30pm - 04:00pm PT

Hall F

Screen: 18

POSTER

Presenter(s)

David Adam, PhD, MS - Johns Hopkins University School of Medicine, Baltimore, MD

D. P. Adam¹, T. Yusufaly², I. R. Marsh¹, R. Bastiaannet³, N. Zaid², A. Chhabra², R. A. Krimins², K. Gabrielson⁴, and R. F. Hobbs¹; ¹Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ²The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, ³Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, ⁴Department of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, MD

Purpose/Objective(s): Evidence is emerging that external beam radiotherapy dose constraints are sometimes insufficient to predict toxicities from radiopharmaceutical therapy (RPT); even standard of care RPT can result in normal tissue toxicities to dose limiting organs like the salivary glands. RPT target agents such as prostate-specific membrane antigen (PSMA) or radioiodine, exhibit non-uniform uptake and subsequently results in ‘sub-voxel’ absorbed dose (AD) non-uniformities that could influence biological outcomes, including toxicities like sialoadenitis and xerostomia. This work develops a small-scale parametrizable computational model of the salivary gland to test the hypothesis that small-scale phenomena may not be encapsulated by conventional RPT dosimetry methods which largely assume uniform voxel or organ-level uptake.

Materials/Methods: Anatomical features of the salivary gland are represented by annular structures (the centralized branching network of ducts, including excretory, lobar, interlobular) and small-scale voxels (intralobular ducts and acinar cells) using dimensions representative of mice and humans. Simulations were performed by scoring and recording AD volume histograms to the target ductal and acinar cells, for two beta emitters (Lu-177, I-131) and one alpha emitter (Ac-225). Four idealized activity distributions were created to assign activity to surface and volumes of the annuli, and a simulation toolkit was used for radiation transport calculations. Comparisons against conventional S-values were conducted to validate the radiation transport and to highlight differences between the small-scale model and conventional dosimetry approaches.

Results: Both the mouse and human model showed much more dosimetric variation in comparison to the homogeneously distributed activity S-value calculation. Among the different permutations of scenarios, the most notable result was that the calculated AD differed between different branches, largely commensurate with the geometric size of the annuli. A greater variability in the ductal cell AD was observed for the human model compared to the mouse model. For the surrounding acinar cells, a substantial proportion of the AD was deposited in the cells nearest the branching structures and the AD was larger as the activity placement was closer to the acinar cells.

Conclusion: Non-uniformity in absorbed dose deposition within the salivary gland highlights the potential utilization of small-scale approaches to RPT dosimetry. Because a substantial proportion of the absorbed dose is deposited less than millimeters from the ductal structure, a prototypical 2 mm voxelized AD grid common in external beam radiotherapy treatments may be inadequate to describe dose-response phenomena. This model provides a concrete computational implementation of such an approach. Future work will further validate the model for pre-clinical translational studies and facilitate salivary gland dosimetry-response predictions in RPT.