title: Propofol decreases in vivo binding of 11C-PBR28 to translocator protein (18 kDa) in the human brain.
abstract: The PET radioligand (11)C-PBR28 targets translocator protein (18 kDa) (TSPO) and is a potential marker of neuroimmune activation in vivo. Although several patient populations have been studied using (11)C-PBR28, no investigators have studied cognitively impaired patients who would require anesthesia for the PET procedure, nor have any reports investigated the effects that anesthesia may have on radioligand uptake. The purpose of this study was to determine whether the anesthetic propofol alters brain uptake of (11)C-PBR28 in healthy subjects.
  
  
  METHODS
  Ten healthy subjects (5 men; 5 women) each underwent 2 dynamic brain PET scans on the same day, first at baseline and then with intravenous propofol anesthesia. The subjects were injected with 680 ± 14 MBq (mean ± SD) of (11)C-PBR28 for each PET scan. Brain uptake was measured as total distribution volume (V(T)) using the Logan plot and metabolite-corrected arterial input function.
  
  
  RESULTS
  Propofol decreased V(T), which corrects for any alteration of metabolism of the radioligand, by about 26% (P = 0.011). In line with the decrease in V(T), brain time-activity curves showed decreases of about 20% despite a 13% increase in plasma area under the curve with propofol. Reduction of V(T) with propofol was observed across all brain regions, with no significant region X condition interaction (P = 0.40).
  
  
  CONCLUSIONS
  Propofol anesthesia reduces the V(T) of (11)C-PBR28 by about 26% in the brains of healthy human subjects. Given this finding, future studies will measure neuroimmune activation in the brains of autistic volunteers and their age and sex-matched healthy controls using propofol anesthesia. We recommend that future PET studies using (11)C-PBR28 and concomitant propofol anesthesia, as would be required in impaired populations, include a control arm to account for the effects of propofol on brain measurements of TSPO.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1026, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Hines
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Zenaide
authors.initials: Z
authors.lastname: Quezado
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Ning
authors.initials: N
authors.lastname: Miao
authors.forename: Maria D
authors.initials: MD
authors.lastname: Ferraris Araneta
authors.forename: Cheryl
authors.initials: C
authors.lastname: Morse
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.forename: Julia
authors.initials: J
authors.lastname: Labovsky
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D000777:Anesthetics / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011743:Pyrimidines / Q000097:blood / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D000777:Anesthetics; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human; D015742:Propofol