Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo [1,5-a]pyrimidin-3-yl acetamide
- 주제(키워드) Translocator protein , Positron emission tomography probe , Structure activity relationships , Neuroinflammation
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Chemistry, Medicinal
- 주제(기타) Chemistry, Organic
- 등재 SCIE, SCOPUS
- 발행기관 PERGAMON-ELSEVIER SCIENCE LTD
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161433
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmc.2019.07.036
- PubMed https://pubmed.ncbi.nlm.nih.gov/31353076
초록/요약
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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