Abstract
[18F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [18F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of Salmonella enterica serovar Typhimurium lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [18F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min). [18F]FEPPA radiosynthesis were carried out in 55 min (from EOB). The non-decay corrected radiochemical yield were 34 ± 2% (n = 17), and the radiochemical purity greater than 99%, with a molar activity of 198 ± 125 GBq/µmol at the end of synthesis. Western blot analysis demonstrated a 2.2-fold increase in TSPO brain expression in the LPS treated mice compared to controls. This was consistent with the significant increase of [18F]FEPPA brain total volume of distribution (VT) estimated with pharmacokinetic modelling. In conclusion, [18F]FEPPA radiosynthesis was implemented with high yields. The new purification/formulation with only class 3 solvents is more suitable for in vivo studies.
Highlights
The translocator protein of 18 kDa (TSPO) is the most advance target for the non-invasive and translational study of inflammatory processes using positron emission tomography (PET)imaging [1]
Signals such as traumatic central nervous system (CNS) injury [9] or bacterial lipopolysaccharide (LPS) [10]. This cellular activation leads to numerous functional and biochemical changes that involve cell morphology, metabolism, cytokine production and some de novo protein synthesis, for instance an increase in the ionized calcium binding adaptor molecule 1 (Iba1) and translocator protein of kDa (TSPO), both used as biomarkers for microglial activation
Radiosynthesis process suitable for clinical use based on previous work of Vasdev et al [33]
Summary
The translocator protein of 18 kDa (TSPO) is the most advance target for the non-invasive and translational study of inflammatory processes using positron emission tomography (PET)imaging [1]. Signals such as traumatic CNS injury [9] or bacterial lipopolysaccharide (LPS) [10]. This cellular activation leads to numerous functional and biochemical changes that involve cell morphology, metabolism, cytokine production and some de novo protein synthesis, for instance an increase in the ionized calcium binding adaptor molecule 1 (Iba1) and TSPO, both used as biomarkers for microglial activation. Microglia can adopt different morphologies and multiple functions: pro-inflammatory or reparative [11,12]. Other glial cells such as astrocytes are activated and may be involved in CNS inflammation [13,14]
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