In vivo variation in metabotropic glutamate receptor subtype 5 binding using positron emission tomography and [11C]ABP688.

Abstract

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-(11)C-methyl-oxime ([(11)C]ABP688), was developed. In this work, eight healthy adult male humans were imaged twice to assess within-subject [(11)C]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 [(11)C]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 [(11)C]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, [(11)C]ABP688 binding variability could make accurate assessments of drug occupancy or group differences using this ligand difficult.

• Authors: Christine DeLorenzo, J S Dileep Kumar, J John Mann, Ramin V Parsey
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 31 Issue 11 Pg. 2169-80 (Nov 2011) ISSN: 1559-7016 [Electronic] United States
• PMID: 21792244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
• Carbon Radioisotopes
• GRM5 protein, human
• Ligands
• Oximes
• Pyridines
• Radiopharmaceuticals
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate

Topics

• Adult
• Animals
• Brain (metabolism)
• Carbon Radioisotopes
• Humans
• Ligands
• Male
• Oximes (pharmacology)
• Papio
• Positron-Emission Tomography
• Protein Binding
• Pyridines (pharmacology)
• Radiochemistry
• Radiopharmaceuticals (pharmacology)
• Receptor, Metabotropic Glutamate 5
• Receptors, Metabotropic Glutamate (antagonists & inhibitors, metabolism)
• Young Adult