PET imaging of glutamate metabolism
L-Glutamate is an abundant amino acid, and a major constituent of proteins.
L-Glutamate is also the predominant excitatory neurotransmitter in the glutamatergic system in central nervous system. Glutamate is concentrated in presynaptic vesicles by active transporters (VGluTs). Glutamate that is released into the synapse is sequestered into neurons and glia by high-affinity glutamate transporters, and metabolized by astrocytes to glutamine. In the presence of decreased extracellular Na+ these transporters can function in reverse, releasing glutamate to the extracellular space. Cystine/glutamate antiporter (system xC-) is vital to antioxidant defence in the brain, and its expression and activity is rapidly upregulated under oxidative stress. Glutamate released by system xC-) activates extrasynaptic, but not synaptic, NMDA iGluRs. During brain ischemia, an excessive release of glutamate triggers neuronal death through the over-activation of NMDA iGluRs. PET imaging with [18F]FSPG has shown increased xC- function in ischemic rats (Soria et al., 2014; Domercq et al., 2016) and in rat model of MS (Martín et al., 2016).
Tracers for Cystine/glutamate antiporter have been developed to study oxidative stress, mainly in tumours, but also in the brain.
Glutamine synthetase activity
[13N]ammonia has been used to measure perfusion, but it also has shown potential in quantification of glutamate metabolism (Cooper, 2011), and specifically glutamine synthetase activity in the brain (Momosaki et al., 2015).
Created at: 2015-08-26
Updated at: 2017-12-04
Written by: Vesa Oikonen