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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

PET Images of the average mGluR5 DVR (0–40 min) using [11C]ABP688 in the three diagnostic groups (n = 14) [107].
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Related In: Results  -  Collection


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fig15: PET Images of the average mGluR5 DVR (0–40 min) using [11C]ABP688 in the three diagnostic groups (n = 14) [107].

Mentions: Cocaine exposure has been reported to reduce mGluR5 expression in the rodent brain [102]. Clinical PET studies were conducted with [11C]ABP688 in cocaine-addicted participants, in comparison with healthy control subjects. [11C]ABP688 binding in the striatum was reduced by approximately 20% in cocaine-addicted participants [103]. Another clinical PET study with [11C]ABP688 demonstrated that mGluR5 availability in cocaine-dependent subjects was inversely proportional to the duration of cocaine abstinence [104]. These studies indicated that distribution of mGluR5 was decreased in the striatum of the living brain in cocaine-abstinent individuals, information that could inform novel strategies for the control of cocaine addiction via mGluR5. Preclinical studies have demonstrated that mGluR5 antagonists potently reduced self-administration of nicotine [105, 106]. In a PET study, a significant reduction in [11C]ABP688 binding was observed in the gray matter of smokers (Figure 15), indicating that mGluR5 could be a potential target for the treatment of nicotine dependence [107]. mGluR5 have been suggested to be involved in the pathophysiology of epilepsy [108, 109]. PET studies using [11C]ABP688 revealed lower levels of mGluR5 binding in the hippocampus and amygdala in rat models of chronic epilepsy, as compared to a control group. Therefore, PET imaging of mGluR5 in the temporal and spatial regions could detect dysregulated glutamatergic networks during epileptogenesis [110]. mGluR5 may also be linked to the pathophysiology of major depression [65]. Clinical PET studies using [11C]ABP688 showed reduced mGluR5 binding in the cortical regions, thalamus, and hippocampus of patients with depression. Furthermore, mGluR5 availability in the hippocampus decreased with the increased severity of this disease, suggesting that changes in the availability of mGluR5 may provide a potential biomarker for the diagnosis of depression [111].


Development of PET and SPECT probes for glutamate receptors.

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

PET Images of the average mGluR5 DVR (0–40 min) using [11C]ABP688 in the three diagnostic groups (n = 14) [107].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig15: PET Images of the average mGluR5 DVR (0–40 min) using [11C]ABP688 in the three diagnostic groups (n = 14) [107].
Mentions: Cocaine exposure has been reported to reduce mGluR5 expression in the rodent brain [102]. Clinical PET studies were conducted with [11C]ABP688 in cocaine-addicted participants, in comparison with healthy control subjects. [11C]ABP688 binding in the striatum was reduced by approximately 20% in cocaine-addicted participants [103]. Another clinical PET study with [11C]ABP688 demonstrated that mGluR5 availability in cocaine-dependent subjects was inversely proportional to the duration of cocaine abstinence [104]. These studies indicated that distribution of mGluR5 was decreased in the striatum of the living brain in cocaine-abstinent individuals, information that could inform novel strategies for the control of cocaine addiction via mGluR5. Preclinical studies have demonstrated that mGluR5 antagonists potently reduced self-administration of nicotine [105, 106]. In a PET study, a significant reduction in [11C]ABP688 binding was observed in the gray matter of smokers (Figure 15), indicating that mGluR5 could be a potential target for the treatment of nicotine dependence [107]. mGluR5 have been suggested to be involved in the pathophysiology of epilepsy [108, 109]. PET studies using [11C]ABP688 revealed lower levels of mGluR5 binding in the hippocampus and amygdala in rat models of chronic epilepsy, as compared to a control group. Therefore, PET imaging of mGluR5 in the temporal and spatial regions could detect dysregulated glutamatergic networks during epileptogenesis [110]. mGluR5 may also be linked to the pathophysiology of major depression [65]. Clinical PET studies using [11C]ABP688 showed reduced mGluR5 binding in the cortical regions, thalamus, and hippocampus of patients with depression. Furthermore, mGluR5 availability in the hippocampus decreased with the increased severity of this disease, suggesting that changes in the availability of mGluR5 may provide a potential biomarker for the diagnosis of depression [111].

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