Development of PSMA-1007-Related Series of <sup>18</sup>F-Labeled Glu-Ureido-Type PSMA Inhibitors
Jens Cardinale, Mareike Roscher, Martin Schäfer, Max Geerlings, Martina Benešová, Ulrike Bauder‐Wüst, Yvonne Remde, Matthias Eder, Zora Nováková, L. Motlova, Cyril Bařinka, Frederik L. Giesel, Klaus Kopka
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 18F-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-rays with mixed results. Among these, PSMA-1007 (compound 5) showed the best interaction with the PSMA protein. The respective radiotracer [18F]PSMA-1007 was translated into the clinic and is, in the meantime, subject of advanced clinical trials.