Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (6): 1206-1207.doi: 10.4103/1673-5374.300432

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Functional imaging of astrocyte activity

Hiroki Kato*, Tatsusada Okuno    

  1. Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, Japan (Kato H)
    Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, Japan (Okuno T)
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Hiroki Kato, MD, PhD, kato-h@umin.org.
  • Supported by:
    The present work was supported by JSPS KAKENHI, Grant Number JP 18K07674 (to HK). 

Abstract: Astrocytes have become known to play a central role in various neuroinflammatory diseases. The evaluation of astrocyte activity using functional imaging is becoming more important. Glucose metabolism or oxygen metabolism in the brain can be assessed using the established clinical imaging methods of F-18 fluorodeoxyglucose positron emission tomography (PET) and O-15 PET, respectively. However, until recently, the highly specific evaluation of metabolic activity in astrocytes has never been applied clinically. Since acetate is selectively taken up and metabolized by astrocytes, its usefulness as a tracer for measuring astrocyte activity has been proposed in basic research. In a human study, the activation of astrocytes associated with neuronal activation has been evaluated in vivo using 1-C-11 acetate PET (Wyss et al., 2009). Astrocytes supply lactate as an energy source to neurons through monocarboxylate transporters (MCTs) and receive and metabolize neurotransmitter glutamate from neurons. The tricarboxylic acid (TCA) cycle in astrocytes provides energy to convert glutamate released from neurons into glutamine as well as newly generating glutamine for neurons. 1-C-11 acetate is selectively taken up by astrocytes mainly by MCT, especially MCT1 and MCT2, and is metabolized by the TCA cycle via acetyl-CoA. Half of the label derived from 1-C-11 acetate is washed out as CO2 in the second round of the TCA cycle in astrocytes, and most of the remaining label is metabolized to glutamate. Considering the short half-life of C-11, metabolites in neurons derived from labeled glutamate, which had been transformed from glutamine passed from the astrocytes, is negligible (Wyss et al., 2009). Therefore, the CO2 washout rate is an index that quantitatively represents the metabolic activity of astrocytes, and the index can be imaged using quantitative PET as the efflux rate of the tracer. Moreover, the tracer accumulation is considered to reflect mainly the labeled glutamine/glutamate pool derived from 1-C-11 acetate. Therefore, 1-C-11 acetate PET can be used to evaluate the central part of astrocyte energy metabolism (Figure 1).