Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide

Van Hieu Tran, Hyunjun Park, Jaekyung Park, Young Do Kwon, Shinwoo Kang, Jae Ho Jung, Keun A. Chang, Byung Chul Lee, Sang Yoon Lee, Soosung Kang, Hee Kwon Kim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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, [18F]11a 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 [18F]DPA-714. An immunohistochemical examination of the dissected brains confirmed that the uptake location of [18F]11a in the PET study was consistent with a positively activated microglia region. This study proved that [18F]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.

Original languageEnglish
Pages (from-to)4069-4080
Number of pages12
JournalBioorganic and Medicinal Chemistry
Issue number18
StatePublished - 15 Sep 2019


  • Neuroinflammation
  • Positron emission tomography probe
  • Structure activity relationships
  • Translocator protein


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