Document Detail


Studies of the metabotropic glutamate receptor 5 radioligand [¹¹C]ABP688 with N-acetylcysteine challenge in rhesus monkeys.
MedLine Citation:
PMID:  23424090     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Detecting changes in receptor binding at the metabotropic glutamate receptor 5 (mGluR5) with the PET allosteric antagonist, [¹¹C]ABP688, may be valuable for studying dysfunctional glutamate transmission associated with psychiatric illnesses. This study was designed to validate the findings of a recent pilot study in baboons which reported a significant global decrease from baseline [¹¹C]ABP688 binding after increasing endogenous glutamate with 50 mg/kg N-acetylcysteine (NAC), with no change from test to retest. In rhesus monkeys (n = 5), paired [¹¹C]ABP688 scans were performed on the same day on the Focus-220 as follows (n = 3 per group): test-retest, baseline-NAC (50 mg/kg), and baseline-NAC (100 mg/kg). Multiple modeling methods were evaluated for kinetic analysis to estimate the total volume of distribution (VT ) and non-displaceable binding potential (BP(ND)) in regions-of-interest (ROIs), with the cerebellum gray matter (CGM) as the reference region. There was an increasing trend from test to retest BP(ND) across ROIs (13%). NAC (50 mg/kg and 100 mg/kg) increased VT (5% and 19%) and decreased BP(ND) (3% and 10%), respectively, significant only for VT in ROIs at the 100 mg/kg dose. High intersubject variability in BP(ND) was comparable to that reported in the baboon study. However, interpretability of BP(ND) is difficult with increases in VT in the CGM reference region at the higher NAC dose. Additionally, the net reduction in BP(ND) from the baseline-NAC scans may be obscured due to observed increases in test-retest BP(ND). Thus, we did not strictly replicate the findings in the baboon study based on BP(ND).
Authors:
Christine M Sandiego; Nabeel Nabulsi; Shu-Fei Lin; David Labaree; Soheila Najafzadeh; Yiyun Huang; Kelly Cosgrove; Richard E Carson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-27
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  67     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-06-24     Completed Date:  2013-11-07     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  489-501     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology*
Animals
Brain / metabolism,  radionuclide imaging
Carbon Radioisotopes / pharmacokinetics,  pharmacology
Female
Macaca mulatta
Male
Oximes / pharmacokinetics,  pharmacology*
Positron-Emission Tomography
Protein Binding / drug effects
Pyridines / pharmacokinetics,  pharmacology*
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors,  metabolism*
Tissue Distribution / drug effects
Grant Support
ID/Acronym/Agency:
1T90DK070068/DK/NIDDK NIH HHS; T90 DK070068/DK/NIDDK NIH HHS; UL1 RR024139/RR/NCRR NIH HHS; UL1 TR000142/TR/NCATS NIH HHS; UL1RR024139/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; 0/Carbon Radioisotopes; 0/Oximes; 0/Pyridines; 0/Receptor, Metabotropic Glutamate 5; 0/Receptors, Metabotropic Glutamate; WYQ7N0BPYC/Acetylcysteine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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