Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antigens, Surface MeSH
- Glutamate Carboxypeptidase II antagonists & inhibitors MeSH
- Humans MeSH
- Ligands MeSH
- Prostatic Neoplasms diagnostic imaging MeSH
- Niacinamide analogs & derivatives chemistry pharmacology MeSH
- Oligopeptides chemistry pharmacology MeSH
- Positron-Emission Tomography MeSH
- Radiopharmaceuticals pharmacology MeSH
- Fluorine Radioisotopes chemistry MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens, Surface MeSH
- FOLH1 protein, human MeSH Browser
- Glutamate Carboxypeptidase II MeSH
- Ligands MeSH
- Niacinamide MeSH
- Oligopeptides MeSH
- PSMA-1007 MeSH Browser
- Radiopharmaceuticals MeSH
- Fluorine Radioisotopes MeSH
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.
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