Limits...
Development of PET and SPECT probes for glutamate receptors.

Fuchigami T, Nakayama M, Yoshida S - ScientificWorldJournal (2015)

Bottom Line: L-glutamate and its receptors (GluRs) play a key role in excitatory neurotransmission within the mammalian central nervous system (CNS).GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to heterotrimeric guanosine nucleotide binding proteins (G-proteins).Although no satisfactory imaging agents have yet been developed for iGluRs, several PET ligands for mGluRs have been successfully employed in clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.

ABSTRACT
L-glutamate and its receptors (GluRs) play a key role in excitatory neurotransmission within the mammalian central nervous system (CNS). Impaired regulation of GluRs has also been implicated in various neurological disorders. GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to heterotrimeric guanosine nucleotide binding proteins (G-proteins). Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of GluRs could provide a novel view of CNS function and of a range of brain disorders, potentially leading to the development of new drug therapies. Although no satisfactory imaging agents have yet been developed for iGluRs, several PET ligands for mGluRs have been successfully employed in clinical studies. This paper reviews current progress towards the development of PET and SPECT probes for GluRs.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of imaging probes for mGluR5.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4385697&req=5

fig10: Chemical structure of imaging probes for mGluR5.

Mentions: Several diaryl alkyne derivatives have been reported as high-affinity, selective mGluR5 antagonists that could be used as in vivo imaging probes. 3-Fluoro-5-(2-pyridinylethynyl) benzonitrile (FPEB, Figure 10) has been reported to have an excellent affinity for mGluR5, with a Ki value of 0.2 nM (rat brain cortex) and a moderate logP value of 2.8. Autoradiography of rhesus monkey brain demonstrated high accumulation in mGluR5-rich regions, such as the cortex, caudate, putamen, amygdala, hippocampus, and most thalamic nuclei, and a low signal in the mGluR5-poor cerebellar layers. In addition, the heterogeneous binding of [18F]FPEB was abolished in the presence of the mGluR5-selective ligand, MPEP, indicating that the radiotracer bound specifically to mGluR5 in vitro [91]. PET studies of [18F]FPEB in rhesus monkey and rat showed similar localization to mGluR5 and displacement by mGluR5 ligands (Figure 11) [91, 92]. Building on these promising preclinical studies of [18F]FPEB, an initial clinical PET study was performed to assess the usefulness of this radiotracer for PET imaging of mGluR5. The regional brain distribution of [18F]FPEB in the healthy adult brain matched the known expression of mGluR5 and showed high reproducibility, suggesting that [18F]FPEB is a suitable PET radioligand for mGluR5 in the human brain [93].


Development of PET and SPECT probes for glutamate receptors.

Fuchigami T, Nakayama M, Yoshida S - ScientificWorldJournal (2015)

Chemical structure of imaging probes for mGluR5.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4385697&req=5

fig10: Chemical structure of imaging probes for mGluR5.
Mentions: Several diaryl alkyne derivatives have been reported as high-affinity, selective mGluR5 antagonists that could be used as in vivo imaging probes. 3-Fluoro-5-(2-pyridinylethynyl) benzonitrile (FPEB, Figure 10) has been reported to have an excellent affinity for mGluR5, with a Ki value of 0.2 nM (rat brain cortex) and a moderate logP value of 2.8. Autoradiography of rhesus monkey brain demonstrated high accumulation in mGluR5-rich regions, such as the cortex, caudate, putamen, amygdala, hippocampus, and most thalamic nuclei, and a low signal in the mGluR5-poor cerebellar layers. In addition, the heterogeneous binding of [18F]FPEB was abolished in the presence of the mGluR5-selective ligand, MPEP, indicating that the radiotracer bound specifically to mGluR5 in vitro [91]. PET studies of [18F]FPEB in rhesus monkey and rat showed similar localization to mGluR5 and displacement by mGluR5 ligands (Figure 11) [91, 92]. Building on these promising preclinical studies of [18F]FPEB, an initial clinical PET study was performed to assess the usefulness of this radiotracer for PET imaging of mGluR5. The regional brain distribution of [18F]FPEB in the healthy adult brain matched the known expression of mGluR5 and showed high reproducibility, suggesting that [18F]FPEB is a suitable PET radioligand for mGluR5 in the human brain [93].

Bottom Line: L-glutamate and its receptors (GluRs) play a key role in excitatory neurotransmission within the mammalian central nervous system (CNS).GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to heterotrimeric guanosine nucleotide binding proteins (G-proteins).Although no satisfactory imaging agents have yet been developed for iGluRs, several PET ligands for mGluRs have been successfully employed in clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.

ABSTRACT
L-glutamate and its receptors (GluRs) play a key role in excitatory neurotransmission within the mammalian central nervous system (CNS). Impaired regulation of GluRs has also been implicated in various neurological disorders. GluRs are classified into two major groups: ionotropic GluRs (iGluRs), which are ligand-gated ion channels, and metabotropic GluRs (mGluRs), which are coupled to heterotrimeric guanosine nucleotide binding proteins (G-proteins). Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of GluRs could provide a novel view of CNS function and of a range of brain disorders, potentially leading to the development of new drug therapies. Although no satisfactory imaging agents have yet been developed for iGluRs, several PET ligands for mGluRs have been successfully employed in clinical studies. This paper reviews current progress towards the development of PET and SPECT probes for GluRs.

No MeSH data available.


Related in: MedlinePlus