Page 38 - I. Chemical biology and drug discovery
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[I. Chemical biology and drug discovery-20]
Synthesis and evaluation of novel fluorinated TSPO ligands
bearing 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide for
PET imaging
Van Hieu Tran¹, Hee-Kwon Kim¹˙*
¹Department of Nuclear Medicine, Jeonbuk National University , Jeonju 54907, Republic of Korea
Neuroinflammation is associated with microglia activation which increased expression of the 18 kDa mitochondrial
translocator protein (TSPO). Positron emission tomography (PET) imaging of microglial activation using TSPO-specific
radioligands was employed to assess disease-associated neuroinflammatory processes. Herein, we have been
developed novel fluorinated TSPO ligands as neuroimaging agents and diagnostic tools for brain inflammation. A
series of TSPO ligands containing 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide structure were prepared. In vitro
binding assay for these newly synthesized ligands was carried out, and it was found that most of the novel ligands
showed a nano-molar affinity for TSPO, which was better than that of DPA-714, which is used in clinical study. In
additions, the most promising ligands 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. This study proved that novel fluorinated TSPO ligands could be
employed as a potential PET tracer for detecting neuroinflammation and neurodegeneration diseases.
