Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET
DC Field | Value | Language |
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dc.contributor.author | Kwon, Young-Do | - |
dc.contributor.author | Kang, Shinwoo | - |
dc.contributor.author | Park, Hyunjun | - |
dc.contributor.author | Cheong, Il-Koo | - |
dc.contributor.author | Chang, Keun-A | - |
dc.contributor.author | Lee, Sang-Yoon | - |
dc.contributor.author | Jung, Jae Ho | - |
dc.contributor.author | Lee, Byung Chul | - |
dc.contributor.author | Lim, Seok Tae | - |
dc.contributor.author | Kim, Hee-Kwon | - |
dc.date.available | 2020-02-27T08:41:44Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2018-11-05 | - |
dc.identifier.issn | 0223-5234 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3059 | - |
dc.description.abstract | Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a-c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were synthesized, and in vitro characterization of each of the novel ligands was performed to elucidate structure activity relationships. All of the newly synthesized ligands displayed nano-molar affinity for TSPO. Particularly, an in vitro affinity study suggests that 2-(5,7-diethyl-2-(4-(3-fluoro-2-methylpropoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (14a), which exhibited high nano-molar affinity for TSPO and proper lipophilicity, was suitable for in vivo brain studies. Thus, radiosynthesis from tosylate precursor 13a using fluorine-18 was performed, and [F-18]14a was obtained in a 31% radiochemical yield (decay-corrected). Dynamic positron emission tomography (PET) imaging studies were performed in a lipopolysaccharide (LPS)-induced neuroinflammation rat model using [F-18]14a to identify the location of inflammation in the brain with a high target-to-background signal ratio. In addition, we validated that the locations of inflammatory lesions found by PET imaging were consistent with the locations observed by histological examination of dissected brains using antibodies. These results suggest that [F-18]14a is a novel promising PET imaging agent for diagnosing neuroinflammation, and it may also prove to be applicable for diagnosing other diseases, including cancers associated with altered TSPO expression, using PET techniques. (C) 2018 Elsevier Masson SAS. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | - |
dc.relation.isPartOf | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.subject | PERIPHERAL BENZODIAZEPINE-RECEPTORS | - |
dc.subject | POSITRON-EMISSION-TOMOGRAPHY | - |
dc.subject | 18 KDA TSPO | - |
dc.subject | IN-VIVO | - |
dc.subject | BIOLOGICAL EVALUATION | - |
dc.subject | HUMAN BRAIN | - |
dc.subject | POLYMORPHISM RS6971 | - |
dc.subject | ACTIVATED MICROGLIA | - |
dc.subject | BINDING-AFFINITY | - |
dc.subject | RAT MODEL | - |
dc.title | Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000449237100023 | - |
dc.identifier.doi | 10.1016/j.ejmech.2018.09.069 | - |
dc.identifier.bibliographicCitation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.159, pp.292 - 306 | - |
dc.identifier.scopusid | 2-s2.0-85054392125 | - |
dc.citation.endPage | 306 | - |
dc.citation.startPage | 292 | - |
dc.citation.title | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 159 | - |
dc.contributor.affiliatedAuthor | Kang, Shinwoo | - |
dc.contributor.affiliatedAuthor | Park, Hyunjun | - |
dc.contributor.affiliatedAuthor | Cheong, Il-Koo | - |
dc.contributor.affiliatedAuthor | Chang, Keun-A | - |
dc.contributor.affiliatedAuthor | Lee, Sang-Yoon | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Translocator protein | - |
dc.subject.keywordAuthor | Positron emission tomography | - |
dc.subject.keywordAuthor | Imaging probe | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordPlus | PERIPHERAL BENZODIAZEPINE-RECEPTORS | - |
dc.subject.keywordPlus | POSITRON-EMISSION-TOMOGRAPHY | - |
dc.subject.keywordPlus | 18 KDA TSPO | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | BIOLOGICAL EVALUATION | - |
dc.subject.keywordPlus | HUMAN BRAIN | - |
dc.subject.keywordPlus | POLYMORPHISM RS6971 | - |
dc.subject.keywordPlus | ACTIVATED MICROGLIA | - |
dc.subject.keywordPlus | BINDING-AFFINITY | - |
dc.subject.keywordPlus | RAT MODEL | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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