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Radiosynthesis and in vivo Evaluation of Carbon‐11 (2 S )‐3‐(1 H ‐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
Author(s) -
Lacivita Enza,
Stama Madia Letizia,
Maeda Jun,
Fujinaga Masayuki,
Hatori Akiko,
Zhang MingRong,
Colabufo Nicola A.,
Perrone Roberto,
Higuchi Makoto,
Suhara Tetsuya,
Leopoldo Marcello
Publication year - 2016
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201500281
Subject(s) - chemistry , in vivo , radiosynthesis , receptor , agonist , positron emission tomography , peptide , imaging agent , b2 receptor , neuroscience , biochemistry , psychology , biology , microbiology and biotechnology , bradykinin
Here, we describe the very first attempt to visualize in vivo formyl peptide receptors ( FPR s) in mouse brain by positron emission tomography ( PET ). FPR s 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 (2 S )‐3‐(1 H ‐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 FPR s receptors in brain slices of PS 19 and APP 23 mice, two animal models of Alzheimer disease. Although ( S )‐[ 11 C]‐ 1 was not suitable to visualize FPR s in the brain, this study provides useful information for the design and characterization of future potential PET radioligands for visualization of brain FPR s by PET .