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Radiosynthesis of a Novel 11 C‐Labeled Derivative of 4’‐ O ‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation
Author(s) -
Kiseleva Mariia M,
Vaulina Daria D,
Sivak Konstantin V,
Alexandrov Andrey G,
Kuzmich Nikolay N,
Viktorov Nikolai B,
Kuznetsova Olga F,
Gomzitalia A
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201904788
Subject(s) - chemistry , neuroinflammation , radiosynthesis , biodistribution , radioligand , in vivo , lipophilicity , ex vivo , radiochemistry , pharmacology , positron emission tomography , stereochemistry , biochemistry , in vitro , nuclear medicine , inflammation , medicine , microbiology and biotechnology , biology
Cyclooxygenase type 2 (COX‐2) is an attractive biomarker for the visualization of neuroinflammation processes by positron emission tomography (PET). Neolignan 4’‐ O ‐methylhonokiol (MH) is known to have high anti‐inflammatory activity and inhibits the expression of COX‐2. We synthesized 4′‐[ 11 C]methoxy‐5‐propyl‐1,1′‐biphenyl‐2‐ol ([ 11 C]MPbP), a compound based on the MH structure and labeled with carbon‐11 (T 1/2 =20.4 min) and studied its distribution in rats treated with lipopolysaccharide (LPS). It was shown that the new ligand has significant inhibitory activity against COX‐2 (IC 50 =0.14 μM) and sufficient lipophilicity (logD 7.4 =2.46±0.12) for penetration the blood brain barrier (BBB). [ 11 C]MPbP was obtained by 11 C‐methylation using [ 11 C]CH 3 I with decay‐corrected radiochemical yield of 20% based on [ 11 C]CH 3 I with molar activity 10–15 GBq/μmol, high radiochemical purity (> 99%) and low level of chemical impurities (<1 μg/ml). The radioligand did not undergo any noticeable decomposition in human plasma for 40 min. The results of ex vivo biodistribution in rats demonstrated that [ 11 C]MPbP crossed the BBB and the observed radioactivity uptake in brain of rats with LPS‐induced neuroinflammation was 4 times higher than in intact animals. Further studies of compounds with the MH scaffold are planned for their possible application in PET, including in vivo assessment in animal neuroinflammation models.