Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein

Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, K(i) = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, K(i) = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing (11)C and (18)F. The syntheses of [(11)C]2a and [(18)F]2b...

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Autores principales: Zhang, Xiang, Jin, Hongjun, Padakanti, Prashanth K., Li, Junfeng, Yang, Hao, Fan, Jinda, Mach, Robert H., Kotzbauer, Paul, Tu, Zhude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310556/
https://www.ncbi.nlm.nih.gov/pubmed/25642331
http://dx.doi.org/10.3390/app4010066
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author Zhang, Xiang
Jin, Hongjun
Padakanti, Prashanth K.
Li, Junfeng
Yang, Hao
Fan, Jinda
Mach, Robert H.
Kotzbauer, Paul
Tu, Zhude
author_facet Zhang, Xiang
Jin, Hongjun
Padakanti, Prashanth K.
Li, Junfeng
Yang, Hao
Fan, Jinda
Mach, Robert H.
Kotzbauer, Paul
Tu, Zhude
author_sort Zhang, Xiang
collection PubMed
description Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, K(i) = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, K(i) = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing (11)C and (18)F. The syntheses of [(11)C]2a and [(18)F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [(11)C]2a and [(18)F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [(11)C]2a in a non-human primate (NHP) confirmed that the tracer was able to cross the BBB with rapid washout kinetics from brain regions of a healthy macaque. The initial studies suggested that further structural optimization of [(11)C]2a and [(18)F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS).
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spelling pubmed-43105562015-01-29 Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein Zhang, Xiang Jin, Hongjun Padakanti, Prashanth K. Li, Junfeng Yang, Hao Fan, Jinda Mach, Robert H. Kotzbauer, Paul Tu, Zhude Appl Sci (Basel) Article Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, K(i) = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, K(i) = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing (11)C and (18)F. The syntheses of [(11)C]2a and [(18)F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [(11)C]2a and [(18)F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [(11)C]2a in a non-human primate (NHP) confirmed that the tracer was able to cross the BBB with rapid washout kinetics from brain regions of a healthy macaque. The initial studies suggested that further structural optimization of [(11)C]2a and [(18)F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS). 2014-03-17 2014-03-17 /pmc/articles/PMC4310556/ /pubmed/25642331 http://dx.doi.org/10.3390/app4010066 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhang, Xiang
Jin, Hongjun
Padakanti, Prashanth K.
Li, Junfeng
Yang, Hao
Fan, Jinda
Mach, Robert H.
Kotzbauer, Paul
Tu, Zhude
Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title_full Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title_fullStr Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title_full_unstemmed Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title_short Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein
title_sort radiosynthesis and in vivo evaluation of two pet radioligands for imaging α-synuclein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310556/
https://www.ncbi.nlm.nih.gov/pubmed/25642331
http://dx.doi.org/10.3390/app4010066
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