title: Radiosynthesis and in vivo Evaluation of Carbon-11 (2S)-3-(1H-Indol-3-yl)-2-{[(4-methoxyphenyl)carbamoyl]amino}-N-{[1-(5-methoxypyridin-2-yl)cyclohexyl]methyl}propanamide: An Attempt to Visualize Brain Formyl Peptide Receptors in Mouse Models of Neuroinflammation.
abstract: Here, we describe the very first attempt to visualize in vivo formyl peptide receptors (FPRs) in mouse brain by positron emission tomography (PET). FPRs are expressed in microglial cells where they mediate chemotactic activity of β-amyloid peptide in Alzheimer disease and, thus, are involved in neuroinflammatory processes. To this purpose, we have selected (2S)-3-(1H-Indol-3-yl)-2-{[(4-methoxyphenyl)carbamoyl]amino}-N-{[1-(5-methoxypyridin-2-yl)cyclohexyl]methyl}propanamide ((S)-1), that we have previously identified as a potent non-peptidic FPR agonist. (S)-[(11) C]-1 has been prepared in high radiochemical yield. (S)-[(11) C]-1 showed very low penetration of blood-brain barrier and, thus, was unable to accumulate into the brain. In addition, (S)-[(11) C]-1 was not able to label FPRs receptors in brain slices of PS19 and APP23 mice, two animal models of Alzheimer disease. Although (S)-[(11) C]-1 was not suitable to visualize FPRs in the brain, this study provides useful information for the design and characterization of future potential PET radioligands for visualization of brain FPRs by PET.
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari. enza.lacivita@uniba.it.
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.
authors.forename: Madia Letizia
authors.initials: ML
authors.lastname: Stama
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.|BIOFORDRUG s.r.l., Spin-off, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Colabufo
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.
authors.forename: Roberto
authors.initials: R
authors.lastname: Perrone
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba, 263-8555, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.|BIOFORDRUG s.r.l., Spin-off, Università degli Studi di Bari 'Aldo Moro', via Orabona, 4, IT-70125, Bari.
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide / Q000378:metabolism*
chemical_list: C000613430:(2S)-3-(1H-indol-3-yl)-2-(((4-methoxyphenyl)carbamoyl)amino)-N-((1-(5-methoxypyridin-2-yl)cyclohexyl)methyl)propanamide; D002250:Carbon Radioisotopes; D007211:Indoles; D011725:Pyridines; D044042:Receptors, Formyl Peptide
keywords: Formyl peptide receptors; Neuroinflammation; PET; Radiosynthesis; Ureidopropanamide