Development of an 18F-labeled azobenzothiazole tracer for α-synuclein aggregates in the brain

Nuclear imaging of aggregated α-synuclein pathology is an urgent clinical need for Parkinson's disease, yet promising tracers for brain α-synuclein aggregates are still rare. In this work, a class of compact benzothiazole derivatives was synthesized and evaluated for α-synuclein aggregates. Amo...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2024-06, Vol.22 (22), p.4550-4558
Main Authors: Wu, Jiajun, Mao, Meiting, Yang, Jie, Li, Kexin, Deng, Pengxin, Zhong, Jing, Wu, Xiaoai, Cheng, Yan
Format: Article
Language:English
Subjects:
Aggregates
Benzothiazole
Brain
Defluorination
Movement disorders
Neurodegenerative diseases
Neuroimaging
Parkinson's disease
Radiolabelling
Synuclein
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Summary:Nuclear imaging of aggregated α-synuclein pathology is an urgent clinical need for Parkinson's disease, yet promising tracers for brain α-synuclein aggregates are still rare. In this work, a class of compact benzothiazole derivatives was synthesized and evaluated for α-synuclein aggregates. Among them, azobenzothiazoles exhibited specific and selective detection of α-synuclein aggregates under physiological conditions. Fluoro-pegylated azobenzothiazole NN-F further demonstrated high-affinity binding to α-synuclein aggregates and efficient 18F-radiolabeling via nucleophilic displacement of a tosyl precursor. [18F]NN-F was stable in plasma in vitro and showed efficient brain uptake with little defluorination in vivo.
ISSN:1477-0520
1477-0539
1477-0539
DOI:10.1039/d4ob00492b