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Development of PSMA-1007-related series of 18F-labeled Glu-Ureido-type PSMA inhibitors

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...

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Main Authors: Cardinale, Jens (Author) , Roscher, Mareike (Author) , Schäfer, Martin (Author) , Geerlings, Max (Author) , Benes̆ová, Martina (Author) , Bauder-Wüst, Ulrike (Author) , Remde, Yvonne (Author) , Eder, Matthias (Author) , Nováková, Zora (Author) , Motlová, Lucia (Author) , Barinka, Cyril (Author) , Giesel, Frederik L. (Author) , Kopka, Klaus (Author)
Format: Article (Journal)
Language:English
Published: August 27, 2020
In: Journal of medicinal chemistry
Year: 2020, Volume: 63, Issue: 19, Pages: 10897-10907
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.9b01479
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jmedchem.9b01479
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Author Notes:Jens Cardinale, Mareike Roscher, Martin Schäfer, Max Geerlings, Martina Benešová, Ulrike Bauder-Wüst, Yvonne Remde, Matthias Eder, Zora Nováková, Lucia Motlová, Cyril Barinka, Frederik L. Giesel, and Klaus Kopka
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Summary: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.
Item Description:Gesehen am 03.02.2021
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.9b01479

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