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Open AccessReview

A Review of Molecular Imaging of Glutamate Receptors

Neuroscience Research Institute, Gachon University, Incheon 21565, Korea
Gachon Advanced Institute for Health Science and Technology, Graduate School, Incheon 21565, Korea
Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Gachon University, Incheon 21565, Korea
ABX Advanced Biochemical Compounds, Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, D-1454 Radeberg, Germany
Centre for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland
Department of Nuclear Medicine, University of Bern, Inselspital, Freiburgstrasse 18, CH-3010 Bern, Switzerland
School of Psychology and Counselling, Queensland University of Technology, Brisbane QLD 4059, Australia
Authors to whom correspondence should be addressed.
Academic Editors: Diego Muñoz-Torrero and Beatriz De Pascual-Teresa
Molecules 2020, 25(20), 4749;
Received: 24 September 2020 / Revised: 13 October 2020 / Accepted: 14 October 2020 / Published: 16 October 2020
Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research. View Full-Text
Keywords: glutamate receptors; positron emission tomography; single photon emission computed tomography; radioligands glutamate receptors; positron emission tomography; single photon emission computed tomography; radioligands
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MDPI and ACS Style

Kim, J.-H.; Marton, J.; Ametamey, S.M.; Cumming, P. A Review of Molecular Imaging of Glutamate Receptors. Molecules 2020, 25, 4749.

AMA Style

Kim J-H, Marton J, Ametamey SM, Cumming P. A Review of Molecular Imaging of Glutamate Receptors. Molecules. 2020; 25(20):4749.

Chicago/Turabian Style

Kim, Jong-Hoon; Marton, János; Ametamey, Simon M.; Cumming, Paul. 2020. "A Review of Molecular Imaging of Glutamate Receptors" Molecules 25, no. 20: 4749.

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