Bivalent Inhibitors of Prostate-Specific Membrane Antigen Conjugated to Desferrioxamine B Squaramide Labeled with Zirconium-89 or Gallium-68 for Diagnostic Imaging of Prostate Cancer.

Autor:	Noor A; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia., Van Zuylekom JK; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia., Rudd SE; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia., Waldeck K; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia., Roselt PD; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia., Haskali MB; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia., Wheatcroft MP; Telix Pharmaceuticals Limited, Suite 401, 55 Flemington Road, North Melbourne, Victoria 3051, Australia., Yan E; Telix Pharmaceuticals Limited, Suite 401, 55 Flemington Road, North Melbourne, Victoria 3051, Australia., Hicks RJ; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia., Cullinane C; Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia., Donnelly PS; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2020 Sep 10; Vol. 63 (17), pp. 9258-9270. Date of Electronic Publication: 2020 Aug 13.
DOI:	10.1021/acs.jmedchem.0c00291
Abstrakt:	Prostate-specific membrane antigen (PSMA) is a carboxypeptidase that is overexpressed in prostate cancer and is an excellent candidate for targeted diagnostic imaging and therapy. Lysine-ureido-glutamate inhibitors of PSMA radiolabeled with positron-emitting radionuclides can be used for diagnostic imaging with positron emission tomography (PET). A squaramide ester derivative of desferrioxamine B (H 3 DFOSq) was used to prepare four new agents with either one or two lysine-ureido-glutamate pharmacophores. The H 3 DFOSq ligand can be used to form stable complexes with either of the positron-emitting radionuclides gallium-68 ( t 1/2 = 68 min) or zirconium-89 ( t 1/2 = 3.3 days). The complexes were evaluated in PSMA-positive xenograft mouse models. Bivalent inhibitors, where two pharmacophores are tethered to a single DFOSq ligand, have better tumor uptake than their monovalent analogues. The ligands presented here, which can be labeled with either gallium-68 or zirconium-89, have the potential to increase the number of clinical sites that can perform diagnostic PET imaging.
Databáze:	MEDLINE
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