Differential influence of propofol and isoflurane anesthesia in non-human primate on the brain kinetics and binding of [$^{18}$F]DPA-714, a PET imaging marker of glial activation

Wadad Saba (1) , Sébastien Goutal (1) , Bertrand Kuhnast (1) , Frédéric Dollé (1) , Sylvain Auvity (1) , Yoan Fontyn (1) , Jérôme Cayla (1) , Marie-Anne Peyronneau (1) , Héric Valette (1) , Nicolas Tournier (2, 1)

1 IMIV - U1023 - ERL9218 - Imagerie Moléculaire in Vivo
2 Université Paris-Saclay

Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of glial cells is related to glial activation. TSPO radioligands such as [$^{18}$F]DPA‐714 are useful for the non‐invasive study of neuroimmune processes using positron emission tomography (PET). Anesthetic agents were shown to impact mitochondrial function and may influence [$^{18}$F]DPA‐714 binding parameters and PET kinetics. [$^{18}$F]DPA‐714 PET imaging was performed in $Papio\ anubis$ baboons anesthetized using either intravenous propofol ($n$ = 3) or inhaled isoflurane ($n$ = 3). Brain kinetics and metabolite‐corrected input function were measured to estimate [$^{18}$F]DPA‐714 brain distribution ($V_T$). Displacement experiments were performed using PK11195 (1.5 mg/kg). In vitro [$^{18}$F]DPA‐714 binding experiments were performed using baboon brain tissue in the absence and presence of tested anesthetics. Brain radioactivity peaked higher in isoflurane‐anesthetized animals compared with propofol (SUVmax = 2.7 ± 0.5 vs. 1.3 ± 0.2, respectively) but was not different after 30 min. Brain $V_T$ was not different under propofol and isoflurane. Displacement resulted in a 35.8 ± 8.4% decrease of brain radioactivity under propofol but not under isoflurane (0.1 ± 7.0%). In vitro, the presence of propofol increased TSPO density and dramatically reduced its affinity for [$^{18}$F]DPA‐714 compared with control. This in vitro effect was not significant with isoflurane. Exposure to propofol and isoflurane differentially influences TSPO interaction with its specific radioligand [$^{18}F$]DPA‐714 with subsequent impact on its tissue kinetics and specific binding estimated in vivo using PET. Therefore, the choice of anesthetics and their potential influence on PET data should be considered for the design of imaging studies using TSPO radioligands, especially in a translational research context.

Mots clés: anesthetic; baboon; in vitro binding; neuroinflammation; peripheral benzodiazepine receptor; positron emission tomography

Domaines: Sciences du Vivant [q-bio]; Neurobiologie; Pharmacologie

Wadad Saba, Sébastien Goutal, Bertrand Kuhnast, Frédéric Dollé, Sylvain Auvity, et al.. Differential influence of propofol and isoflurane anesthesia in non-human primate on the brain kinetics and binding of [$^{18}$F]DPA-714, a PET imaging marker of glial activation. European Journal of Neuroscience, 2015, 42, pp.1738-1745. ⟨10.1111/ejn.12946⟩. ⟨cea-02937752⟩