Pharmacokinetic and dosimetry modeling of Radiopharmaceutical Therapy using Spatial Transcriptomics in microenvironment

The efficacy of radiopharmaceutical therapy (RPT) relies on the ability to deliver cytotoxic radiation to cancer cells or the surrounding tumor microenvironment (TME) while minimizing normal tissue toxicity. Therefore, dosimetry is essential to understand the factors that influence treatment. The spatial transcriptomics (ST) technique may offer a breakthrough in investigating RPT dosimetry as it enables to spatially profile the diverse gene transcripts that are associated with TME. In this study, we propose a novel approach to combine the pharmacokinetics and dosimetry of RPT with ST maps to elucidate the heterogeneity of RPT dosimetry and its effects. For proof of concept, we focused on modeling 177Lu-and 225Ac-prostate-specific membrane antigen (PSMA), which emit beta and alpha particles, respectively. Specifically, we solved partial differential equations (PDE) of the pharmacokinetic model and applied the dose-voxel kernel (DVK) method using various ST maps. Additionally, assuming hypoxia as one of the influencing factors in RPT, we utilized hypoxia ST to measure the cell survival probability of each 177Lu-and 225Ac- RPT.