In vitro and in vivo evaluation of [18F]-FDEGPECO as a PET tracer for imaging the metabotropic glutamate receptor subtype 5 (mGluR5)

NeuroImage ◽  
2011 ◽  
Vol 56 (3) ◽  
pp. 984-991 ◽  
Author(s):  
Cindy A. Wanger-Baumann ◽  
Linjing Mu ◽  
Michael Honer ◽  
Sara Belli ◽  
Malte F. Alf ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtype ◽  
In Vivo Evaluation ◽  
Metabotropic Glutamate ◽  
Pet Tracer

Radiolabeling and in vitro and in vivo evaluation of [18F]-FE-DABP688 as a PET radioligand for the metabotropic glutamate receptor subtype 5

2007 ◽  
Vol 34 (8) ◽  
pp. 973-980 ◽  
Author(s):  
Michael Honer ◽  
Anja Stoffel ◽  
Lea J. Kessler ◽  
P. August Schubiger ◽  
Simon M. Ametamey
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtype ◽  
In Vivo Evaluation ◽  
Metabotropic Glutamate

scholarly journals Acute Ketamine Infusion in Rat Does Not Affect In Vivo [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5

2018 ◽  
Vol 17 ◽  
pp. 153601211878863 ◽  
Author(s):  
Lauren Kosten ◽  
Jeroen Verhaeghe ◽  
Leonie wyffels ◽  
Sigrid Stroobants ◽  
Steven Staelens
Keyword(s):  
Nmda Receptor ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Acute Effect ◽  
Receptor Subtype ◽  
Ketamine Infusion ◽  
Metabotropic Glutamate ◽  
Pet Tracer

Detecting changes in metabotropic glutamate receptor 5 (mGluR5) availability through molecular imaging with the positron emission tomography (PET) tracer [11C]ABP688 is valuable for studying dysfunctional glutamate transmission associated with neuropsychiatric disorders. Using an infusion protocol in rats, we visualized the acute effect of subanesthetic doses of ketamine on mGluR5 in rat brain. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist known to increase glutamate release. Imaging was performed with a high-affinity PET ligand [11C]ABP688, a negative allosteric modulator of mGluR5. Binding did not change significantly from baseline to ketamine in any region, thereby confirming previous literature with other NMDA receptor antagonists in rodents. Hence, in rats, we could not reproduce the findings in a human setup showing significant decreases in the [11C]ABP688 binding after a ketamine bolus followed by ketamine infusion. Species differences may have contributed to the different findings in the present study of rats. In conclusion, we could not confirm in rats that endogenous glutamate increases by ketamine infusion are reflected in [11C]ABP688 binding decreases as was previously shown for humans.

scholarly journals in vivo Variation in Metabotropic Glutamate Receptor Subtype 5 Binding Using Positron Emission Tomography and [11C]ABP688

2011 ◽  
Vol 31 (11) ◽  
pp. 2169-2180 ◽  
Author(s):  
Christine DeLorenzo ◽  
J S Dileep Kumar ◽  
J John Mann ◽  
Ramin V Parsey
Keyword(s):  
Positron Emission Tomography ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Preliminary Evidence ◽  
Emission Tomography ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
Pet Tracer ◽  
Positron Emission

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders. Recently, a positron emission tomography (PET) tracer exhibiting high selectivity and specificity for mGluR5, 3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime ([11C]ABP688), was developed. In this work, eight healthy adult male humans were imaged twice to assess within-subject [11C]ABP688 binding variability using PET. In seven of the eight subjects, significantly higher binding was observed during the second (retest) scan. This binding increase could not be definitively explained by differences in ligand injected mass or dose, or changes in metabolism between scans. In addition, this type of systematic binding increase was not observed in a [11C]ABP688 test–retest study performed by our group on anaesthetized baboons. It is therefore possible that the increased binding was because of physiological changes occurring between scans, such as changes in endogenous glutamate levels. If PET imaging with [11C]ABP688 could detect such differences, as preliminary evidence suggests, it could be used to help uncover the role of glutamate in the pathophysiology of brain disorders. However, regardless of its ability to detect endogenous glutamate differences, [11C]ABP688 binding variability could make accurate assessments of drug occupancy or group differences using this ligand difficult.

scholarly journals Ketamine and Ceftriaxone-Induced Alterations in Glutamate Levels Do Not Impact the Specific Binding of Metabotropic Glutamate Receptor Subtype 5 Radioligand [18F]PSS232 in the Rat Brain

2018 ◽  
Vol 11 (3) ◽  
pp. 83 ◽  
Author(s):  
Adrienne Müller Herde ◽  
Silvan Boss ◽  
Yingfang He ◽  
Roger Schibli ◽  
Linjing Mu ◽  
...  
Keyword(s):  
Rat Brain ◽  
Glutamate Receptor ◽  
Bolus Injection ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
In Vitro Autoradiography ◽  
Direct Competition

Several studies showed that [11C]ABP688 binding is altered following drug-induced perturbation of glutamate levels in brains of humans, non-human primates and rats. We evaluated whether the fluorinated derivative [18F]PSS232 can be used to assess metabotropic glutamate receptor 5 (mGluR5) availability in rats after pharmacological challenge with ketamine, known to increase glutamate, or ceftriaxone, known to decrease glutamate. In vitro autoradiography was performed on rat brain slices with [18F]PSS232 to prove direct competition of the drugs for mGluR5. One group of rats were challenged with a bolus injection of either vehicle, racemic ketamine, S-ketamine or ceftriaxone followed by positron emission tomography PET imaging with [18F]PSS232. The other group received an infusion of the drugs during the PET scan. Distribution volume ratios (DVRs) were calculated using a reference tissue model. In vitro autoradiography showed no direct competition of the drugs with [18F]PSS232 for the allosteric binding site of mGluR5. DVRs of [18F]PSS232 binding in vivo did not change in any brain region neither after bolus injection nor after infusion. We conclude that [18F]PSS232 has utility for measuring mGluR5 density or occupancy of the allosteric site in vivo, but it cannot be used to measure in vivo fluctuations of glutamate levels in the rat brain.

Sign in / Sign up

Export Citation Format

Share Document