title: Differential influence of propofol and isoflurane anesthesia in a non-human primate on the brain kinetics and binding of [(18)F]DPA-714, a positron emission tomography imaging marker of glial activation.
abstract: 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 (VT). 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 VT 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.
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Wadad
authors.initials: W
authors.lastname: Saba
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Goutal
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Kuhnast
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Auvity
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Fontyn
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cayla
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Peyronneau
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Héric
authors.initials: H
authors.lastname: Valette
authors.affiliation: Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tournier
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009457:Neuroglia / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D015742:Propofol / Q000494:pharmacology*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*
chemical_list: D018681:Anesthetics, General; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019788:Fluorodeoxyglucose F18; D007530:Isoflurane; D015742:Propofol
keywords: anesthetic; baboon; in vitro binding; neuroinflammation; peripheral benzodiazepine receptor; positron emission tomography