2581 - Bridging Organ-Level and Microscale Dosimetry: A 3D Histology-Informed Model of the Renal Cortex for Alpha-Emitting Radionuclides
Presenter(s)
B. President1, R. J. Dawson2, N. Zaid3, W. Bolch2, and R. F. Hobbs4; 1Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2University of Florida, Gainesville, FL, 3The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 4Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose/Objective(s): Alpha-emitting radiopharmaceutical therapies (RPTs) offer potent tumor control by remaining confined to the intended source region because of its short range (50 – 100 microns) and creation of irreparable double-strand breaks, but kidney toxicity can limit dosing. Standard dosimetry uses whole-organ models, missing microscale energy deposition in critical structures. The human kidney contains roughly one million nephrons per organ, which are non-replicating functional units. Radiation-induced loss of nephrons leads to permanent decline in renal function, whereas damage to renal tubular cells can be transient, as these cells retain the ability to regenerate. Consequently, the distinction between permanent and temporary renal impairment depends on the relative contributions of nephron loss versus tubular cell injury. This study sought to establish a histology-informed three-dimensional model of the renal cortical labyrinth to support microscale alpha-particle dosimetry.
Materials/Methods: Serial histologic sections of human renal cortex were examined and digitally imaged at 10x magnification and reconstructed into a volumetric dataset in 3D Slicer. Renal corpuscles and major cortical structures were segmented, with glomeruli delineated by outer borders and centerline points mapped across consecutive sections to trace proximal and distal tubules. Segmentations were exported to Rhinoceros 3D to generate anatomically realistic polygon mesh models. Glomeruli were sized based on measured diameters, and tubules reconstructed using diameter-specific centerline extrusions, corrected for fixation-induced shrinkage via scaling derived from red blood cell measurements. Monte Carlo simulations in PHITS evaluated alpha-particle transport for multiple source–target configurations and source distributions (uniform, linear, exponential), with S-values calculated using dedicated post-processing routines.
Results: An approximate 1 mm³ cortical volume was reconstructed, incorporating seven intact renal corpuscles with associated proximal and distal tubules. Remaining volume was populated with tubular fragments and interstitial components (blood and extracellular space) based on compositions found in literature. Alpha-particle S-values were successfully generated for multiple therapeutic radionuclides and microanatomic source–target combinations, demonstrating the feasibility of resolving dose deposition at the level of individual functional renal substructures.
Conclusion: This histology-derived 3D renal cortical model enables microscale alpha-particle dosimetry within anatomically realistic nephron components. By bridging the gap between organ-level dose estimates and tissue-level energy deposition, this methodology provides a foundation for improving renal toxicity prediction and patient-specific treatment planning in alpha-emitting RPTs.