FOLH1 and neoplasm: To evaluate the structure–activity relationship, hydrophobic linker modifications were performed on the same basic chemical construct, which demonstrates that (1) multiple aromatic rings in the linker fragment improved the hydrophobic interaction with S1-accessory pocket suitable for PSMA-specific cell surface binding and cell internalization, (2) a rigid aromatic modification (2-naphthyl-l-alanine) in the linker benefited the PSMA-specific cell internalization, and (3) incorporation of 2-naphthyl-l-Ala-AMCH showed an optimal tumor-to-background ratio [73].