Abstract
In recent years, a number of drugs targeting the prostate specific-membrane antigen (PSMA) have become important tools in the diagnosis and treatment of prostate cancer. In the present work, we report on the synthesis and preclinical evaluation of a series of (18)F-labeled PSMA ligands for diagnostic application based on the theragnostic ligand PSMA-617.
By applying modifications to the linker-structure, insight into the structure-activity relationship could be gained highlighting the importance of hydrophilicity and stereoselectivity on interaction with PSMA and hence the biodistribution. Selected compounds were co-crystallized with the PSMA-protein and analyzed by X-ray with mixed results.
Amongst these, PSMA-1007 (compound 5) showed the best interaction with the PSMA protein. The respective radiotracer [(18)F]PSMA-1007 was translated into the clinic and is in the meantime subject of advanced clinical trials.