| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Shukuri Miho (日) (読)
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| 2. | (英) Mawatari Aya (日) (読)
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| 3. | (英) Takatani Shuhei (日) (読)
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| 4. | 田原 強 ([徳島大学.先端研究推進センター.バイオイメージング研究部門])
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| 5. | (英) Inoue Michiko (日) (読)
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| 6. | (英) Arakaki Wakako (日) (読)
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| 7. | (英) Ohno Masahiro (日) (読)
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| 8. | (英) Doi Hisashi (日) (読)
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| 9. | (英) Onoe Hirotaka (日) (読)
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| ○題名 (必須): | □ | (英) Synthesis and preclinical evaluation of 18F-FKTP methyl ester as a radiotracer for COX-1 imaging in neuroinflammation (日)
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| ○要約 (任意): | □ | (英) Cyclooxygenase (COX) is a rate-limiting enzyme in the synthesis of proinflammatory prostanoids from arachidonic acid. In vivo imaging of COX by PET is a potentially powerful tool for assessing the inflammatory response to injury, infection, and disease. We previously reported on a promising PET probe for COX imaging, C-labeled ketoprofen methyl ester, which can detect COX-1 activation in models of neuroinflammation and neurodegenerative disorders. In the current study, we aimed to design a fluorine-substituted benzoyl group of ketoprofen (FKTP) and to evaluate its racemate and enantiomers (F-labeled ketoprofen methyl ester, [F]FKTP-Me) as PET proradiotracers, potential radiopharmaceuticals for in vivo PET study of COX-1. We performed nucleophilic aromatic F-fluorination to obtain the desired racemic radiolabeled probe, ()-[F]FKTP-Me, at a radiochemical yield of 11%-13%. Subsequent high-performance liquid chromatography separation with a chiral column yielded the desired enantiomerically pure ()- and ()-[F]FKTP-Me. We examined the in vivo properties of ()-, ()-, and ()-[F]FKTP-Me in PET studies using rats in which hemispheric inflammation was induced by intrastriatally injecting a lipopolysaccharide. Racemic ()-[F]FKTP-Me and enantiomeric ()- or ()-[F]FKTP-Me were synthesized with radiochemical and chemical purities of more than 99%. The metabolite analysis revealed that the racemic ()-[F]FKTP-Me crossed the blood-brain barrier and entered the brain, where it was subsequently hydrolyzed to its pharmacologically active acid form. PET images revealed a high accumulation of ()-, ()-, and ()-[F]FKTP in the inflamed regions in rat brain. Moreover, the accumulated radioactivity of ()-[F]FKTP-Me was higher than that of ()-[F]FKTP-Me and ()-[F]FKTP-Me, which was correlated with the stereospecific inhibitory activity of FKTP against COX-1. From the results of this study, we conclude that racemic ()-[F]FKTP-Me and its enantiomers could act as proradiotracers of neuroinflammation in rat brain by the association of their hydrolyzed acid forms with COX-1 in inflamed regions. In particular, ()-[F]FKTP-Me demonstrated suitable properties as a COX-1-specific probe in PET imaging of neuroinflammation. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Rats (日) (読)
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| 3. | (英) Cyclooxygenase 1 (日) (読)
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| 4. | (英) Ketoprofen (日) (読)
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| 5. | (英) Neuroinflammatory Diseases (日) (読)
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| 6. | (英) Positron-Emission Tomography (日) (読)
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| 7. | (英) Radiopharmaceuticals (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Journal of Nuclear Medicine (Society of Nuclear Medicine)
(pISSN: 0161-5505, eISSN: 1535-5667)
| ○ISSN (任意): | □ | 1535-5667
ISSN: 0161-5505
(pISSN: 0161-5505, eISSN: 1535-5667) Title: Journal of nuclear medicine : official publication, Society of Nuclear MedicineTitle(ISO): J Nucl MedPublisher: Society of Nuclear Medicine and Molecular Imaging (NLM Catalog)
(Scopus)
(CrossRef)
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| ○巻 (必須): | □ | 63
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| ○号 (必須): | □ | 11
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| ○頁 (必須): | □ | 1761 1767
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2022年 11月 初日 (令和 4年 11月 初日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.2967/jnumed.121.263713 (→Scopusで検索)
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| ○PMID (任意): | □ | 35332095 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.2967/jnumed.121.263713 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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| 4. | (英) KeywordList.Keyword: COX-1 (日)
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| 5. | (英) KeywordList.Keyword: PET (日)
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| 6. | (英) KeywordList.Keyword: [18F]FKTP-Me (日)
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| 7. | (英) KeywordList.Keyword: neuroinflammation (日)
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