Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [F-18] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy) pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamideLacivita, E., Lucente, E., Kwizera, C., Farinha Antunes, I., Niso, M., De Giorgio, P., Perrone, R., Colabufo, N. A., Elsinga, P. H. & Leopoldo, M., 1-Jan-2017, In : Bioorganic & Medicinal Chemistry. 25, 1, p. 277-292 16 p.
Research output: Contribution to journal › Article › Academic › peer-review
Gastrin-releasing peptide receptors (GRP-Rs, also known as bombesin 2 receptors) are overexpressed in a variety of human cancers, including prostate cancer, and therefore they represent a promising target for in vivo imaging of tumors using positron emission tomography (PET). Structural modifications of the nonpeptidic GRP-R antagonist PD-176252 ((S)-1a) led to the identification of the fluorinated analog (S)-3(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy) pyridin-2-yl] cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl) ureido] propionamide ((S)-1m) that showed high affinity and antagonistic properties for GRP-R. This antagonist was stable in rat plasma and towards microsomal oxidative metabolism in vitro. (S)-1m was successfully radiolabeled with fluorine-18 through a conventional radiochemistry procedure. [F-18] (S)-1m showed high affinity and displaceable interaction for GRP-Rs in PC3 cells in vitro. (C) 2016 Elsevier Ltd. All rights reserved.
|Number of pages||16|
|Journal||Bioorganic & Medicinal Chemistry|
|Publication status||Published - 1-Jan-2017|
- Gastrin-releasing peptide, Positron emission tomography, Prostate cancer, Molecular imaging, G-protein coupled receptors, PROSTATE-CANCER, BOMBESIN RECEPTORS, AGONISTS, ANTAGONISTS, ANALOGS, EXPRESSION, BREAST