Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors
- 27 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 63 (19), 10897-10907
- https://doi.org/10.1021/acs.jmedchem.9b01479
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-ray with mixed results. Amongst 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.Keywords
Funding Information
- Bundesministerium f?r Bildung und Forschung (01DR17031A, 2U2WTZKOREA-021)
- European Regional Development Fund (CZ.1.05/1.1.00/02.0109)
- Grantov? Agentura Cesk? Republiky (18-04790S)
- Chinese Academy of Sciences (RVO: 86652036)
This publication has 50 references indexed in Scilit:
- Glu-Ureido–Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic RadiotracersJournal of Nuclear Medicine, 2017
- Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patientsEuropean Journal of Nuclear Medicine and Molecular Imaging, 2017
- Radiolabeled prostate-specific membrane antigen small-molecule inhibitorsThe Quarterly Journal of Nuclear Medicine and Molecular Imaging, 2017
- 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography for prostate cancer imaging: A narrative literature reviewWorld Journal of Nuclear Medicine, 2017
- The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate CancerJournal of Nuclear Medicine, 2016
- Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CTEuropean Journal of Nuclear Medicine and Molecular Imaging, 2016
- New Clinical Indications for 18 F/ 11 C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the LiteratureEuropean Urology, 2016
- Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with 68Ga-PSMA-HBED-CC than with 18F-Fluoroethylcholine PET/CTEuropean Journal of Nuclear Medicine and Molecular Imaging, 2016
- Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancerEuropean Journal of Nuclear Medicine and Molecular Imaging, 2013
- [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECHEuropean Journal of Nuclear Medicine and Molecular Imaging, 2012