Abstract
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Objectives To investigate whether PET imaging of the microglial activation marker Translocator Protein (TSPO) can be used to detect changes in microglial activation during experimental endotoxemia in nonhuman primates.
Methods Six female baboons (Papio anubis) received intravenous administration of E. coli endotoxin (0.1 mg/kg). The PET ligand [11C]PBR28 was used to measure changes in TSPO binding from baseline to 1, 4, and 24 hrs after endotoxin administration. Regional time-activity data from brain regions of interest were fitted to a two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (VT) of [11C]PBR28 was estimated from the model fits and used as a measure of total tracer binding. Change in VT from baseline was used as a measure of microglial activation. Serum interleukin-6 (IL-6) was used as a measure of endotoxemic severity.
Results Endotoxin administration was associated with a ~1,000-fold increase in serum IL-6 levels, indicating a robust innate immune response to endotoxin. Consistent with our a priori hypothesis, there was an increase (range 11%-100%) in whole-brain [11C]PBR28 VT at 1 and 4 hrs after endotoxin administration.
Conclusions Intravenous administration of bacterial endotoxin is associated with an increase in total binding (VT) of the TSPO radiotracer [11C]PBR28, suggesting that experimental endotoxemia in nonhuman primates can cause microglial activation that can be measured with PET imaging. This is the first study to show that an experimental intervention can modulate TSPO expression to a degree that can be measured with PET.
Research Support The Society for Nuclear Medicine and the Department of the Army (W81XWH-08-2-0701; JH) provided funding. The information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred