Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-¹¹C-acetate

The purpose of this study was to investigate astrocytic oxidative metabolism using 1-¹¹C-acetate. 1-¹¹C-acetate kinetics were evaluated in the rat somatosensory cortex using a β-scintillator during different manipulations (test-retest, infraorbital nerve stimulation, and administration of acetazolamide or dichloroacetate). In humans a visual activation paradigm was used and kinetics were measured with positron emission tomography. Data were analyzed using a one-tissue compartment model. The following features supported the hypothesis that washout of radiolabel (k ₂) is because of ¹¹C-CO₂ and therefore related to oxygen consumption (CMRO₂): (1) the onset of ¹¹C washout was delayed; (2) k₂ was not affected by acetazolamide-induced blood flow increase; (3) k₂ demonstrated a significant increase during stimulation in rats (from 0.014±0.007 to 0.027±0.006 per minute) and humans (from 0.016±0.010 to 0.026±0.006 per minute); and (4) dichloroacetate led to a substantial decrease of k₂. In the test-retest experiments K₁ and k₂ were very stable. In summary, 1-¹¹C-acetate seems a promising tracer to investigate astrocytic oxidative metabolism in vivo. If the washout rate indeed represents the production of ¹¹C-CO₂, then its increase during stimulation would point to a substantially higher astrocytic oxidative metabolism during brain activation. However, the quantitative relationship between k₂ and CMRO₂ needs to be determined in future experiments.