New Scaffolds and Multifunctional Intermediates for Imaging PSMA

The prostate-specific membrane antigen (PSMA) is increasingly recognized as an important target for cancer imaging and therapy. Current PSMA inhibitors based on a urea scaffold have shown good results for imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) in human subjects. The urea scaffold has certain limitations, including undesired renal uptake and other non-specific (non-tumor) binding. Twenty seven new urea-based scaffolds were synthesized and studied with respect to their binding affinity to PSMA. Two high affinity compounds were successfully radiolabeled and injected into mice with PSMA+ tumors. The images demonstrate advantages over the earlier compounds at earlier time points, e.g., more rapid renal clearance. The carbamate and reversed carbamate scaffolds may complement the existing urea and other scaffolds upon which inhibitors, imaging and therapeutic agents targeting PSMA have been based.

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