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Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide
- Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide
- Van Hieu Tran; Park, Hyunjun; Park, Jaekyung; Kwon, Young-Do; Kang, Shinwoo; Jung, Jae Ho; Chang, Keun-A; Lee, Byung Chul; Lee, Sang-Yoon; Kang, Soosung; Kim, Hee-Kwon
- Ewha Authors
- Issue Date
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY
- BIOORGANIC & MEDICINAL CHEMISTRY vol. 27, no. 18, pp. 4069 - 4080
- Translocator protein; Positron emission tomography probe; Structure activity relationships; Neuroinflammation
- PERGAMON-ELSEVIER SCIENCE LTD
- SCIE; SCOPUS
- Document Type
- Translocator protein (TSPO) expression is closely related with neuroinflammation and neuronal damage which might cause several central nervous system diseases. Herein, a series of TSPO ligands (11a-c and 13a-d) with a 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide structure were prepared and evaluated via an in vitro binding assay. Most of the novel ligands exhibited a nano-molar affinity for TSPO, which was better than that of DPA-714. Particularly, 11a exhibited a subnano-molar TSPO binding affinity with suitable lipophilicity for in vivo brain studies. After radiolabeling with fluorine-18, [F-18] 11a Filla was used for a dynamic positron emission tomography (PET) study in a rat LPS-induced neuroinflammation model; the inflammatory lesion was clearly visualized with a superior target-to-background ratio compared to [F-18]DPA-714. An immunohistochemical examination of the dissected brains confirmed that the uptake location of [F-18] 11a in the PET study was consistent with a positively activated microglia region. This study proved that [F-18] 11a could be employed as a potential PET tracer for detecting neuroinflammation and could give possibility for diagnosis of other diseases, such as cancers related with TSPO expression.
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