Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors
| Autor: | Frederik L. Giesel, Yvonne Remde, Max Geerlings, Matthias Eder, Martina Benešová, Cyril Barinka, Klaus Kopka, Lucia Motlova, Ulrike Bauder-Wüst, Mareike Roscher, Martin Schäfer, Jens Cardinale, Zora Novakova |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Biodistribution Chemistry urologic and male genital diseases medicine.disease 01 natural sciences 0104 chemical sciences 010404 medicinal & biomolecular chemistry 03 medical and health sciences Prostate cancer Drug Discovery Cancer research medicine Molecular Medicine Linker 030304 developmental biology Membrane antigen |
| Zdroj: | Journal of Medicinal Chemistry. 63:10897-10907 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.9b01479 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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