Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [(11)C]ABP688 PET.
OBJECTIVE
Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals.


METHODS
Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere.


RESULTS
We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction.


CONCLUSIONS
The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada. jonathan.dubois@mail.mcgill.ca.
Jonathan M
JM
DuBois
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
Olivier G
OG
Rousset
Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Jared
J
Rowley
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada.
Manuel
M
Porras-Betancourt
PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada.|Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK.
Andrew J
AJ
Reader
Department of Epidemiology, Biostatistics and Occupational health, McGill University, Montreal, Canada.|Department of Psychiatry, Douglas Mental Health University Institute / Douglas Institut Universitaire en Santé Mentale, Montreal, Canada.
Aurelie
A
Labbe
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada.
Gassan
G
Massarweh
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada.
Jean-Paul
JP
Soucy
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada.|Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Pedro
P
Rosa-Neto
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada. eliane.kobayashi@mcgill.ca.
Eliane
E
Kobayashi
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010091:Oximes; D049268:Positron-Emission Tomography; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012727:Sex Characteristics; D055815:Young Adult
C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
Healthy controls; Metabotropic glutamate receptor 5; Positron emission tomography; [11C]ABP688