Propofol decreases in vivo binding of ¹¹C-PBR28 to translocator protein (18 kDa) in the human brain

The PET radioligand ¹¹C-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 ¹¹C-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 ¹¹C-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 ¹¹C-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). Conclusion: Propofol anesthesia reduces the V_T of ¹¹C-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 ¹¹C-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.