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Molecules 2018, 23(6), 1375; https://doi.org/10.3390/molecules23061375

[18F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model

1
Assistance Publique—Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, 75010 Paris, France
2
Inserm UMR-S 1144, Faculté de Pharmacie de Paris, Université Paris Descartes, 75006 Paris, France
3
Assistance Publique—Hôpitaux de Paris, Hôpital Universitaire Necker—Enfants Malades, 75015 Paris, France
4
Institut Universitaire d’Hématologie, Université Paris Diderot, 75013 Paris, France
5
Assistance Publique—Hôpitaux de Paris, Hôpital Cochin, 75014 Paris, France
6
Assistance Publique—Hôpitaux de Paris, Hôpital Lariboisière, Médecine Nucléaire, 75010 Paris, France
7
Inserm UMR-S 942, Université Paris Diderot, 75013 Paris, France
*
Author to whom correspondence should be addressed.
Received: 24 April 2018 / Revised: 25 May 2018 / Accepted: 4 June 2018 / Published: 7 June 2018
(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)
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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. View Full-Text
Keywords: [18F]FEPPA; TSPO; brain inflammation; small-animal PET imaging; radiolabeling; radiotracer metabolism [18F]FEPPA; TSPO; brain inflammation; small-animal PET imaging; radiolabeling; radiotracer metabolism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Vignal, N.; Cisternino, S.; Rizzo-Padoin, N.; San, C.; Hontonnou, F.; Gelé, T.; Declèves, X.; Sarda-Mantel, L.; Hosten, B. [18F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model. Molecules 2018, 23, 1375.

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