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

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• 作者：Enza Lacivita^a ; Ermelinda Lucente^a ; ¹ ; Chantal Kwizera^b ; Ines F. Antunes^b ; Mauro Niso^a ; Paola De Giorgio^a ; Roberto Perrone^a ; ^c ; Nicola A. Colabufo^a ; ^c ; Philip H. Elsinga^b ; Marcello Leopoldo^a ; ^c ; ^{marcello.leopoldo@uniba.it}
• 关键词：GRP ; gastrin-releasing peptide ; CNS ; central nervous system ; PET ; positron emission tomography
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：277-292
• 全文大小：2255 K
• 卷排序：25

文摘

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.