Optimizing PSMA-617-based inhibitors through charged linker modifications: Insights into structure-activity relationships

. While some modifications led to improved tumor-to-kidney ratios and favorable early-stage excretion, it remains challenging to predict clinical off-targeting effects like salivary gland uptake. This study provides important insights into the structure-activity relationships of PSMA-617-related linker modifications and warrant additional investigation, including mechanistic and translational studies, to more accurately evaluate their therapeutic potential.