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

Translocator protein 18  kD a ( 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 PK 11195 (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 ( SUV max  = 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.