Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation
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′‐[11C]methox...
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| Veröffentlicht in: | ChemistrySelect (Weinheim) 2020-03, Vol.5 (9), p.2685-2689 |
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| creator | Kiseleva, Mariia M Vaulina, Daria D Sivak, Konstantin V Alexandrov, Andrey G Kuzmich, Nikolay N Viktorov, Nikolai B Kuznetsova, Olga F Gomzina, Natalia A |
| description | 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′‐[11C]methoxy‐5‐propyl‐1,1′‐biphenyl‐2‐ol ([11C]MPbP), a compound based on the MH structure and labeled with carbon‐11 (T1/2=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 (IC50=0.14 μM) and sufficient lipophilicity (logD7.4=2.46±0.12) for penetration the blood brain barrier (BBB). [11C]MPbP was obtained by 11C‐methylation using [11C]CH3I with decay‐corrected radiochemical yield of 20% based on [11C]CH3I with molar activity 10–15 GBq/μmol, high radiochemical purity (> 99%) and low level of chemical impurities ( |
| doi_str_mv | 10.1002/slct.201904788 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley</sourceid><recordid>TN_cdi_wiley_primary_10_1002_slct_201904788_SLCT201904788</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>SLCT201904788</sourcerecordid><originalsourceid>FETCH-wiley_primary_10_1002_slct_201904788_SLCT2019047883</originalsourceid><addsrcrecordid>eNqlj0FOwzAQRS0EEhXtlvVcoMVOkzRZhyKQ0lK13VuGTBSDY6PYDcquR2BX9Xo9CQ5CFXsWo5nR_P9Hj5BbRieM0uDOqlc3CShLaThLkgsyCKZxNI6jML38M1-TkbVvlFIWJ3EQzQbksBaFNLbTrkIrLZgSBCxNiwoYy077r1y8oMIC7rGRrXCyxV4TnvZHf3z2tUBXdaoy2rxLo0DoAp6chVWDStZSi6aDeSvUznuNBqm9AvLVBtbCwcIU_pHPW-KuMVKXStT1j3BIrkqhLI5--w1JH-bb7HH8KRV2_KORtU_mjPIen_f4_IzPN3m2PW_T_3i_AWEnbgI</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation</title><source>Access via Wiley Online Library</source><creator>Kiseleva, Mariia M ; Vaulina, Daria D ; Sivak, Konstantin V ; Alexandrov, Andrey G ; Kuzmich, Nikolay N ; Viktorov, Nikolai B ; Kuznetsova, Olga F ; Gomzina, Natalia A</creator><creatorcontrib>Kiseleva, Mariia M ; Vaulina, Daria D ; Sivak, Konstantin V ; Alexandrov, Andrey G ; Kuzmich, Nikolay N ; Viktorov, Nikolai B ; Kuznetsova, Olga F ; Gomzina, Natalia A</creatorcontrib><description>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′‐[11C]methoxy‐5‐propyl‐1,1′‐biphenyl‐2‐ol ([11C]MPbP), a compound based on the MH structure and labeled with carbon‐11 (T1/2=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 (IC50=0.14 μM) and sufficient lipophilicity (logD7.4=2.46±0.12) for penetration the blood brain barrier (BBB). [11C]MPbP was obtained by 11C‐methylation using [11C]CH3I with decay‐corrected radiochemical yield of 20% based on [11C]CH3I 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 [11C]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.
Novel radiolabeled 4’‐O‐methylhonokiol derivative [11C]MPbP with good radiochemical yield and high radiochemical purity was obtained. In vitro measured biological properties as well as ex vivo biodistribution studies of the new radioligand in LPS induced rats showed a high potential of compounds with the 4’‐O‐methylhonokiol scaffold for imaging neuroinflammatory processes.</description><identifier>ISSN: 2365-6549</identifier><identifier>EISSN: 2365-6549</identifier><identifier>DOI: 10.1002/slct.201904788</identifier><language>eng</language><subject>biodistribution ; carbon-11 ; cyclooxygenase 2 (COX-2) ; inflammation ; radiopharmaceuticals</subject><ispartof>ChemistrySelect (Weinheim), 2020-03, Vol.5 (9), p.2685-2689</ispartof><rights>2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-4554-6125</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fslct.201904788$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fslct.201904788$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Kiseleva, Mariia M</creatorcontrib><creatorcontrib>Vaulina, Daria D</creatorcontrib><creatorcontrib>Sivak, Konstantin V</creatorcontrib><creatorcontrib>Alexandrov, Andrey G</creatorcontrib><creatorcontrib>Kuzmich, Nikolay N</creatorcontrib><creatorcontrib>Viktorov, Nikolai B</creatorcontrib><creatorcontrib>Kuznetsova, Olga F</creatorcontrib><creatorcontrib>Gomzina, Natalia A</creatorcontrib><title>Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation</title><title>ChemistrySelect (Weinheim)</title><description>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′‐[11C]methoxy‐5‐propyl‐1,1′‐biphenyl‐2‐ol ([11C]MPbP), a compound based on the MH structure and labeled with carbon‐11 (T1/2=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 (IC50=0.14 μM) and sufficient lipophilicity (logD7.4=2.46±0.12) for penetration the blood brain barrier (BBB). [11C]MPbP was obtained by 11C‐methylation using [11C]CH3I with decay‐corrected radiochemical yield of 20% based on [11C]CH3I 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 [11C]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.
Novel radiolabeled 4’‐O‐methylhonokiol derivative [11C]MPbP with good radiochemical yield and high radiochemical purity was obtained. In vitro measured biological properties as well as ex vivo biodistribution studies of the new radioligand in LPS induced rats showed a high potential of compounds with the 4’‐O‐methylhonokiol scaffold for imaging neuroinflammatory processes.</description><subject>biodistribution</subject><subject>carbon-11</subject><subject>cyclooxygenase 2 (COX-2)</subject><subject>inflammation</subject><subject>radiopharmaceuticals</subject><issn>2365-6549</issn><issn>2365-6549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqlj0FOwzAQRS0EEhXtlvVcoMVOkzRZhyKQ0lK13VuGTBSDY6PYDcquR2BX9Xo9CQ5CFXsWo5nR_P9Hj5BbRieM0uDOqlc3CShLaThLkgsyCKZxNI6jML38M1-TkbVvlFIWJ3EQzQbksBaFNLbTrkIrLZgSBCxNiwoYy077r1y8oMIC7rGRrXCyxV4TnvZHf3z2tUBXdaoy2rxLo0DoAp6chVWDStZSi6aDeSvUznuNBqm9AvLVBtbCwcIU_pHPW-KuMVKXStT1j3BIrkqhLI5--w1JH-bb7HH8KRV2_KORtU_mjPIen_f4_IzPN3m2PW_T_3i_AWEnbgI</recordid><startdate>20200306</startdate><enddate>20200306</enddate><creator>Kiseleva, Mariia M</creator><creator>Vaulina, Daria D</creator><creator>Sivak, Konstantin V</creator><creator>Alexandrov, Andrey G</creator><creator>Kuzmich, Nikolay N</creator><creator>Viktorov, Nikolai B</creator><creator>Kuznetsova, Olga F</creator><creator>Gomzina, Natalia A</creator><scope/><orcidid>https://orcid.org/0000-0002-4554-6125</orcidid></search><sort><creationdate>20200306</creationdate><title>Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation</title><author>Kiseleva, Mariia M ; Vaulina, Daria D ; Sivak, Konstantin V ; Alexandrov, Andrey G ; Kuzmich, Nikolay N ; Viktorov, Nikolai B ; Kuznetsova, Olga F ; Gomzina, Natalia A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-wiley_primary_10_1002_slct_201904788_SLCT2019047883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>biodistribution</topic><topic>carbon-11</topic><topic>cyclooxygenase 2 (COX-2)</topic><topic>inflammation</topic><topic>radiopharmaceuticals</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiseleva, Mariia M</creatorcontrib><creatorcontrib>Vaulina, Daria D</creatorcontrib><creatorcontrib>Sivak, Konstantin V</creatorcontrib><creatorcontrib>Alexandrov, Andrey G</creatorcontrib><creatorcontrib>Kuzmich, Nikolay N</creatorcontrib><creatorcontrib>Viktorov, Nikolai B</creatorcontrib><creatorcontrib>Kuznetsova, Olga F</creatorcontrib><creatorcontrib>Gomzina, Natalia A</creatorcontrib><jtitle>ChemistrySelect (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiseleva, Mariia M</au><au>Vaulina, Daria D</au><au>Sivak, Konstantin V</au><au>Alexandrov, Andrey G</au><au>Kuzmich, Nikolay N</au><au>Viktorov, Nikolai B</au><au>Kuznetsova, Olga F</au><au>Gomzina, Natalia A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation</atitle><jtitle>ChemistrySelect (Weinheim)</jtitle><date>2020-03-06</date><risdate>2020</risdate><volume>5</volume><issue>9</issue><spage>2685</spage><epage>2689</epage><pages>2685-2689</pages><issn>2365-6549</issn><eissn>2365-6549</eissn><abstract>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′‐[11C]methoxy‐5‐propyl‐1,1′‐biphenyl‐2‐ol ([11C]MPbP), a compound based on the MH structure and labeled with carbon‐11 (T1/2=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 (IC50=0.14 μM) and sufficient lipophilicity (logD7.4=2.46±0.12) for penetration the blood brain barrier (BBB). [11C]MPbP was obtained by 11C‐methylation using [11C]CH3I with decay‐corrected radiochemical yield of 20% based on [11C]CH3I 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 [11C]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.
Novel radiolabeled 4’‐O‐methylhonokiol derivative [11C]MPbP with good radiochemical yield and high radiochemical purity was obtained. In vitro measured biological properties as well as ex vivo biodistribution studies of the new radioligand in LPS induced rats showed a high potential of compounds with the 4’‐O‐methylhonokiol scaffold for imaging neuroinflammatory processes.</abstract><doi>10.1002/slct.201904788</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-4554-6125</orcidid></addata></record> |
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| subjects | biodistribution carbon-11 cyclooxygenase 2 (COX-2) inflammation radiopharmaceuticals |
| title | Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation |
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