Publication
Title
Longitudinal characterization of mGluR5 using -ABP688 PET imaging in the Q175 mouse model of Huntington's disease
Author
Abstract
The metabotropic glutamate receptor type 5 (mGluR5) represents a potential therapeutic target for the treatment of Huntingtons disease (HD). Using 11C-ABP688, a non-competitive and highly selective antagonist for mGluR5, we aimed to longitudinally characterize in vivo changes of mGluR5 by means of PET imaging in the Q175 mouse model of HD. Methods: 11C-ABP688 PET imaging, followed by an X-ray computed tomography (CT) scan, was performed in heterozygous Q175 mice (n = 18) and wild-type (WT) littermates (n = 18) at three different time points (namely 6, 9, and 13 months of age). 11C-ABP688 binding potential (BPND) was calculated for each time point in striatum and cortex using the cerebellum as reference region. In addition, voxel-based statistical parametric mapping (SPM) analysis was performed on BPND images. Post-mortem validation of mGluR5 levels and neuronal density was performed at 6 months of age. Results: 11C-ABP688 BPND of heterozygous Q175 animals was significantly reduced at all time points in the striatum (6 months: -13.1%, P < 0.001, 9 months: -13.5%, P < 0.001, and 13 months: -14.2%, P < 0.001) and in the cortex (6 months: -9.8%, P < 0.01, 9 months: -10.2%, P < 0.01, and 13 months: -10.6%, P < 0.01) when compared to WT littermates. Longitudinal changes of 11C-ABP688 BPND were also found in heterozygous mice showing a reduction at 13 months compared to 6 months (-10.4%, P < 0.05). SPM analysis confirmed reduced BPND in heterozygous compared to WT as well as the time-related decline of 11C-ABP688 binding in the striatum of heterozygous Q175 mice. Post-mortem analysis confirmed mGluR5 decrease in both striatum (-36.6%; P < 0.01) and cortex (-16.6%; P < 0.05) of heterozygous Q175 mice, while no difference in neuronal density was found. Conclusion: In vivo imaging of mGluR5 using 11C-ABP688 PET/CT revealed a marked reduction of ligand binding in the striatum and cortex of heterozygous mice compared to WT animals as well as a temporal decline in heterozygous Q175 mice. This study suggests 11C-ABP688 PET imaging as potential biomarker to monitor the disease progression and therapeutic strategies in HD.
Language
English
Source (journal)
The Journal of nuclear medicine. - New York
The Journal of nuclear medicine. - New York
Publication
New York : 2018
ISSN
0161-5505
Volume/pages
59 :11 (2018) , p. 1722-1727
ISI
000448962500016
Pubmed ID
29794227
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Translocator protein expression in an animal model of temporal lobe epilepsy.
Translocator protein expression in animal models of temporal lobe epilepsy and Huntington's Disease.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 02.10.2018
Last edited 20.09.2021
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