Radiosynthesis of carbon-11 and fluorine-18 labelled radiotracers to image the ionotropic and metabotropic glutamate receptors*

摘要

As the major excitatory neurotransmitter in the central nervous system (CNS), L-glutamate mediates its pharmacological action through the activation of both ionotropic and metabotropic receptor families.1 The ionotropic glutamate receptors (iGluRs)2 defined as ligand-gated cation channels are named after their first known selective agonist (Figure 1): AZ-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-Tsoxazolepropionic acid (AMPA) and (2S,3S,4S)-2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine (kainate) receptors. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors divided in three groups: group I (mGluRI and 5) coupled to Gq/Gn and activating phospholipase C; and group II (mGluR2 and 3) and group III (mGluRs 4,6, 7 and 8) coupled to Gi/O inhibiting adenylyl cyclase and coupled also with other signal pathways such as activation of mitogen-activated protein kinase.3