Mesh-based detailed human kidney models of the ICRP reference adults for radiopharmaceutical therapy dosimetry: microscale model of the renal cortex

Abstract Objective: Radiopharmaceutical therapy (RPT) is a rapidly evolving field in oncology, driven by advances in molecular targeting, such as prostate-specific membrane antigen (PSMA), and the use of radionuclides with different radiation emissions, including beta emitters and alpha emitters. RPT is typically used to treat disseminated cancers, where dosimetry-based treatment planning aims to limit radiation exposure to normal organs and reduce toxicity. This study aimed to develop a three-dimensional, histology-informed model of the human renal cortical labyrinth to support microscale dosimetry and the development of dose-response models for renal toxicity in RPT. The microscale model was dosimetrically coupled to an improved macroscale kidney model within the ICRP reference adult male and female phantoms. Approach: Histological human kidney sections were serially imaged using a high-resolution digital camera mounted on a light microscope. The images were imported into 3D Slicer for volumetric reconstruction. Renal corpuscles were manually segmented, and convoluted tubules were mapped using centerline luminal markers. Glomeruli were reconstructed by stitching segmented slices and scaling them to match diameters measured in 3D Slicer. Bowman's capsules were modeled to surround each glomerulus. Proximal and distal convoluted tubules (PCTs and DCTs) were created using a multi-pipe function. Main results: The final microscale model included seven renal corpuscles with their respective PCTs and DCTs, embedded within a representative microenvironment containing tubule fragments, blood vessels, and extracellular tissue. Absorbed fractions were calculated for multiple source-target combinations. These microscale dosimetry results were coupled with corresponding macroscale kidney dosimetry to generate S-values for more than 1200 radionuclides. Significance: A three-dimensional, histology-informed model of the human renal cortical labyrinth was developed from H&E-stained kidney sections to represent the principal components of the nephron and its surrounding microenvironment. Coupling the microscale and macroscale models provides a framework for evaluating radionuclide-specific energy deposition at both spatial scales.