Original Article
Journal of Cerebral Blood Flow & Metabolism (2009) 29, 44–56; doi:10.1038/jcbfm.2008.86; published online 20 August 2008
Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate
The study was supported by the Swiss National Science Foundation (Grants 3100A0-105804/1 and PP00B-110751/1) and by the OPO-Stiftung Zürich.
Matthias T Wyss1, Bruno Weber1,2, Valerie Treyer1, Stefan Heer1, Luc Pellerin3, Pierre J Magistretti4 and Alfred Buck1
- 1PET Center, Division of Nuclear Medicine, University Hospital, Zürich, Switzerland
- 2Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland
- 3Physiology Department, University of Lausanne, Lausanne, Switzerland
- 4Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
Correspondence: Dr A Buck, Division of Nuclear Medicine, Rämistrasse 100, University Hospital, Zürich CH-8091, Switzerland. E-mail: fred.buck@usz.ch
Received 16 November 2007; Revised 27 June 2008; Accepted 27 June 2008; Published online 20 August 2008.
Abstract
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 
-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 (k2) 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 0.0270.006 per minute) and humans (from 0.0160.010 to 0.0260.006 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.
Keywords:
1-11C-acetate, astrocytes, -scintillator, oxidative metabolism, positron emission tomography, washout
