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-(11)C-acetate. 1-(11)C-acetate kinetics were evaluated in the rat somatosensory cortex using a beta-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 (11)C-CO(2) and therefore related to oxygen consumption (CMRO(2)): (1) the onset of (11)C washout was delayed; (2)k(2) was not affected by acetazolamide-induced blood flow increase; (3)k(2) 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 k(2). In the test-retest experiments K(1) and k(2) were very stable. In summary, 1-(11)C-acetate seems a promising tracer to investigate astrocytic oxidative metabolism in vivo. If the washout rate indeed represents the production of (11)C-CO(2), then its increase during stimulation would point to a substantially higher astrocytic oxidative metabolism during brain activation. However, the quantitative relationship between k(2) and CMRO(2) needs to be determined in future experiments.
Wyss
Matthias T
MT
PET Center, Division of Nuclear Medicine, University Hospital, Zürich, Switzerland.
Weber
Bruno
B
Treyer
Valerie
V
Heer
Stefan
S
Pellerin
Luc
L
Magistretti
Pierre J
PJ
Buck
Alfred
A
D000085:Acetates / Q000494:pharmacology*; D000086:Acetazolamide / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D049268:Positron-Emission Tomography; D051381:Rats; D015203:Reproducibility of Results
D000085:Acetates; D002250:Carbon Radioisotopes; D000086:Acetazolamide