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Current Radioligands for the PET Imaging of Metabotropic Glutamate Receptors

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PET and SPECT of Neurobiological Systems

Abstract

Glutamate receptors are divided into two main groups: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). Modulation of iGluRs and mGluRs has potential for the treatment of psychiatric and neurological diseases such as depression, anxiety, schizophrenia, and Parkinson’s disease. Positron emission tomography (PET) might offer the possibility to visualize glutamate receptors and presents an interesting tool for studying these receptors under physiologic and pathologic conditions. MGluR PET radioligands reported till April 2012 are outlined alongside their in vitro/in vivo properties and clinical applications. Emphasis is given to mGluR1 and mGluR5, two receptor subtypes for which most advances in radioligand development have been accomplished.

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Abbreviations

ABP688:

3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enonemethyl-oxime

AMPA:

2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)-propionic acid

BBB:

Blood-brain barrier

B max :

Maximal binding capacity

BPND :

Binding potential relative to the no displaceable compartment

Bq:

Becquerel

BSA:

Bovine serum albumin

CAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

DMF:

Dimethylformamide

DMSO:

Dimethyl sulfoxide

EOB:

End of bombardment

EOS:

End of synthesis

Et3N:

Triethylamine

GPCR:

G-protein-coupled receptor

HBD:

Hydrogen bond donors

HPLC:

High-pressure liquid chromatography

i.v:

Intravenous

IC50 :

Inhibition constant required for displacement of 50 % of radioligand binding

ID:

Injected dose

IDnorm./g:

Injected dose normalized to body weight per tissue weight

iGluR:

Ionotropic glutamate receptor

K d :

Dissociation constant

K i :

Inhibition constant

ko:

Knockout

LTP:

Long-term potentiation

MeI:

Methyl iodide

M-FPEP:

2-methyl-6-(3-fluoro-phenylethynyl)-pyridine

mGluR:

Metabotropic glutamate receptor

mGluR5:

Metabotropic glutamate receptor subtype 5

min:

Minute(s)

M-MPEP:

2-methyl-6-((methoxyphenyl)ethynyl)-pyridine

MPEP:

6-methyl-2-(phenylethynyl)-pyridine

MW:

Microwave

NAC:

N-acetylcysteine

NMDA:

N-methyl-d-aspartate

NMDAR:

N-methyl-d-aspartate receptor

p.i.:

Postinjection

PBS:

Phosphate buffered saline

PET:

Positron emission tomography

P-gp:

P-glycoprotein

PI:

Phosphoinositol

PLC:

Phospholipase C

ROI:

Region of interest

RT:

Room temperature

SAR:

Structure–activity relationship

SUV:

Standard uptake value

TAC:

Time activity curve

TEMPO:

2,2,6,6-tetramethylpiperidine-1-oxyl

THF:

Tetrahydrofuran

TM:

Transmembrane domain

TPSA:

Topological polar surface area

wt:

Wild-type

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Authors and Affiliations

  1. Department of Nuclear Medicine, Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, University Hospital Zürich, CH-8091, Zürich, Switzerland

    Linjing Mu

  2. Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, ETH Zurich, CH-8093, Zurich, Switzerland

    Simon M. Ametamey

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  1. Linjing Mu
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Correspondence to Simon M. Ametamey .

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Editors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering and Information Technology, University of Applied Sciences Offenburg, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Molecular Neurobiology, Universtiy of Groningen, Groningen, The Netherlands

    Paul G.M. Luiten

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Mu, L., Ametamey, S.M. (2014). Current Radioligands for the PET Imaging of Metabotropic Glutamate Receptors. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Luiten, P. (eds) PET and SPECT of Neurobiological Systems. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-42014-6_15

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