2. Academic Validation
  3. Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [18F] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide

Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [18F] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide

  • Bioorg Med Chem. 2017 Jan 1;25(1):277-292. doi: 10.1016/j.bmc.2016.10.031.
Enza Lacivita 1,  Ermelinda Lucente 1,  Chantal Kwizera 2,  Ines F Antunes 2,  Mauro Niso 1,  Paola De Giorgio 1,  Roberto Perrone 3,  Nicola A Colabufo 3,  Philip H Elsinga 2,  Marcello Leopoldo 4
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy.
  • 2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • 3 Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy; BIOFORDRUG s.r.l., Spin-off, Università degli Studi di Bari Aldo Moro, Bari, Italy.
  • 4 Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy; BIOFORDRUG s.r.l., Spin-off, Università degli Studi di Bari Aldo Moro, Bari, Italy. Electronic address: [email protected].
PMID: 27863916 DOI: 10.1016/j.bmc.2016.10.031
Abstract

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 non-peptidic 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. [18F](S)-1m showed high affinity and displaceable interaction for GRP-Rs in PC3 cells in vitro.

Keywords

G-protein coupled receptors; Gastrin-releasing peptide; Molecular imaging; Positron emission tomography; Prostate cancer.

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