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 Neuroinfl
| Autor: | Masayuki Fujinaga, Marcello Leopoldo, Akiko Hatori, Roberto Perrone, Makoto Higuchi, Ming-Rong Zhang, Madia Letizia Stama, Nicola Antonio Colabufo, Tetsuya Suhara, Enza Lacivita, Jun Maeda |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Indoles Pyridines medicine.drug_class Stereochemistry Mice Transgenic Bioengineering Peptide Biochemistry Rats Sprague-Dawley Mice Radioligand Assay 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Humans Carbon Radioisotopes Receptor Molecular Biology Inflammation Neurons chemistry.chemical_classification Molecular Structure Radiosynthesis Brain Chemotaxis General Chemistry General Medicine Receptors Formyl Peptide Propanamide Rats Disease Models Animal 030104 developmental biology chemistry Positron-Emission Tomography Molecular Medicine Caco-2 Cells 030217 neurology & neurosurgery |
| Zdroj: | Chemistry & Biodiversity. 13:875-883 |
| ISSN: | 1612-1872 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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