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

11 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

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education , Republic of Korea ( 2018R1D1A1B07047572 ). This work was supported by Fund of Biomedical Research Institute, Chonbuk National University Hospital , Republic of Korea. This work was supported by a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health and Welfare , Republic of Korea ( HI14C1135 ).

Publisher Copyright:
© 2019 Elsevier Ltd


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


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