Predictive Value of Pre-treatment Ga-68 PSMA-11 PET/CT Volumetric Parameters for Toxicity in Lu-177 PSMA-617 Therapy

The aim of this study was to evaluate the relationship between volumetric parameters obtained from pre-treatment Gallium-68-labeled PSMA-11 (Ga-68 PSMA-11) PET/CT imaging and the development of nephrotoxicity and hematotoxicity during treatment in patients receiving Lutetium-177-labeled PSMA-617 (Lu-177 PSMA-617) radioligand therapy (RLT), and to investigate the potential of these parameters to predict toxicity. Forty-three patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) who underwent Lu-177 PSMA-617 RLT were included in the study. The patients’ baseline clinical characteristics, previous treatment history, and pre-treatment and treatment-related nephrological and hematological parameters were retrospectively recorded. Pre-RLT Ga-68 PSMA-11 PET/CT images were analyzed using LIFEx software. Regions of interest (ROIs) were created using a threshold value of 40% of the maximum Standard Uptake Value for metastatic lesions, and volumetric parameters were calculated. Organ-specific volumetric parameters for the kidneys and spleen were obtained using a similar method. Decreases in laboratory parameters were analyzed as absolute and percentage changes. Statistical analyses were performed using SPSS v25; relationships between variables were evaluated using univariate/multivariate linear regression and Spearman correlation analyses. A significant relationship was found between kidney-derived volumetric PSMA parameters and absolute and percentage changes in kidney function. Volumetric parameters reflecting metastatic tumor burden showed a significant correlation with the decrease in hematological parameters. Toxicity-related changes were more limited in oligometastatic patients compared to non-oligometastatic patients. Volumetric parameters obtained from pre-treatment Ga-68 PSMA-11 PET/CT imaging can be used as valuable biomarkers for predicting serious nephrological and hematological toxicities that may develop during Lu-177 PSMA-617 therapy.