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Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy

[Image: see text] In this study, we synthesized four novel Al(18/19)F-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral a...

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Autores principales: Song, Jia, Peng, Xiaohui, Li, Linlin, Yang, Fan, Zhang, Xiaojun, Zhang, Jinming, Dai, Jiapei, Cui, Mengchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217595/
https://www.ncbi.nlm.nih.gov/pubmed/30411027
http://dx.doi.org/10.1021/acsomega.8b01120
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author Song, Jia
Peng, Xiaohui
Li, Linlin
Yang, Fan
Zhang, Xiaojun
Zhang, Jinming
Dai, Jiapei
Cui, Mengchao
author_facet Song, Jia
Peng, Xiaohui
Li, Linlin
Yang, Fan
Zhang, Xiaojun
Zhang, Jinming
Dai, Jiapei
Cui, Mengchao
author_sort Song, Jia
collection PubMed
description [Image: see text] In this study, we synthesized four novel Al(18/19)F-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to Aβ(1–42) aggregates, of which complex 17 possessing the most potent affinity (K(i) = 11.3 nM) was selected for further biological evaluations. In vitro fluorescent staining and in vitro autoradiography studies on brain sections from CAA patients proved that this ligand could label Aβ deposits in blood vessels selectively. In biodistribution study, [(18)F]17 can hardly penetrate the blood–brain barrier (brain(2 min) = 0.3% ID/g) and displayed a rapid blood washout rate (blood(2 min)/blood(60 min) = 25.2), which is favorable as CAA imaging agents. In conclusion, this Al(18)F-labeled 2-phenylbenzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent.
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spelling pubmed-62175952018-11-06 Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy Song, Jia Peng, Xiaohui Li, Linlin Yang, Fan Zhang, Xiaojun Zhang, Jinming Dai, Jiapei Cui, Mengchao ACS Omega [Image: see text] In this study, we synthesized four novel Al(18/19)F-labeled 2-phenylbenzothiazole derivatives conjugated to 1,4,7-triazacyclononane-1,4-diacetic acid via alkyl linkers and evaluated them as imaging agent targets to amyloid-β (Aβ) plaques deposited in the blood vessels of cerebral amyloid angiopathy (CAA) brain. The four ligands exhibited moderate-to-high binding ability to Aβ(1–42) aggregates, of which complex 17 possessing the most potent affinity (K(i) = 11.3 nM) was selected for further biological evaluations. In vitro fluorescent staining and in vitro autoradiography studies on brain sections from CAA patients proved that this ligand could label Aβ deposits in blood vessels selectively. In biodistribution study, [(18)F]17 can hardly penetrate the blood–brain barrier (brain(2 min) = 0.3% ID/g) and displayed a rapid blood washout rate (blood(2 min)/blood(60 min) = 25.2), which is favorable as CAA imaging agents. In conclusion, this Al(18)F-labeled 2-phenylbenzothiazole complex was developed and proved to be a promising CAA positron emission tomography agent. American Chemical Society 2018-10-12 /pmc/articles/PMC6217595/ /pubmed/30411027 http://dx.doi.org/10.1021/acsomega.8b01120 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Song, Jia
Peng, Xiaohui
Li, Linlin
Yang, Fan
Zhang, Xiaojun
Zhang, Jinming
Dai, Jiapei
Cui, Mengchao
Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title_full Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title_fullStr Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title_full_unstemmed Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title_short Al(18)F-NODA Benzothiazole Derivatives as Imaging Agents for Cerebrovascular Amyloid in Cerebral Amyloid Angiopathy
title_sort al(18)f-noda benzothiazole derivatives as imaging agents for cerebrovascular amyloid in cerebral amyloid angiopathy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217595/
https://www.ncbi.nlm.nih.gov/pubmed/30411027
http://dx.doi.org/10.1021/acsomega.8b01120
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