TY - JOUR
T1 - 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
T2 - An Attempt to Visualize Brain Formyl Peptide Receptors in Mouse Models of Neuroinflammation
AU - Lacivita, Enza
AU - Stama, Madia Letizia
AU - Maeda, Jun
AU - Fujinaga, Masayuki
AU - Hatori, Akiko
AU - Zhang, Ming Rong
AU - Colabufo, Nicola A.
AU - Perrone, Roberto
AU - Higuchi, Makoto
AU - Suhara, Tetsuya
AU - Leopoldo, Marcello
N1 - Publisher Copyright:
© 2016 Wiley-VHCA AG, Zürich
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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)-[11C]-1 has been prepared in high radiochemical yield. (S)-[11C]-1 showed very low penetration of blood–brain barrier and, thus, was unable to accumulate into the brain. In addition, (S)-[11C]-1 was not able to label FPRs receptors in brain slices of PS19 and APP23 mice, two animal models of Alzheimer disease. Although (S)-[11C]-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.
AB - 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)-[11C]-1 has been prepared in high radiochemical yield. (S)-[11C]-1 showed very low penetration of blood–brain barrier and, thus, was unable to accumulate into the brain. In addition, (S)-[11C]-1 was not able to label FPRs receptors in brain slices of PS19 and APP23 mice, two animal models of Alzheimer disease. Although (S)-[11C]-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.
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U2 - 10.1002/cbdv.201500281
DO - 10.1002/cbdv.201500281
M3 - Article
C2 - 27251949
AN - SCOPUS:84978386324
SN - 1612-1872
SP - 875
EP - 883
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
ER -