Sex differences in [11C]ABP688 binding: a positron emission tomography study of mGlu5 receptors

Kelly Smart; Sylvia M L Cox; Stephanie G Scala; Maria Tippler; Natalia Jaworska; Michel Boivin; Jean R Séguin; Chawki Benkelfat; Marco Leyton

doi:10.1007/s00259-018-4252-4

Sex differences in [¹¹C]ABP688 binding: a positron emission tomography study of mGlu5 receptors

Eur J Nucl Med Mol Imaging. 2019 May;46(5):1179-1183. doi: 10.1007/s00259-018-4252-4. Epub 2019 Jan 9.

Authors

Kelly Smart¹, Sylvia M L Cox¹, Stephanie G Scala¹, Maria Tippler¹, Natalia Jaworska^{2

3}, Michel Boivin⁴, Jean R Séguin^{5

6}, Chawki Benkelfat^{1

7}, Marco Leyton^{8

9

10

11

12}

Affiliations

¹ Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, QC, H3A 1A1, Canada.
² Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
³ Institute of Mental Health Research, affiliated with the University of Ottawa, Ottawa, ON, K1Z 7K4, Canada.
⁴ Department of Psychology, Université Laval, Quebec City, QC, G1V 0A6, Canada.
⁵ CHU Ste-Justine Research Center, Montreal, QC, H3T 1C5, Canada.
⁶ Department of Psychiatry and Addiction, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
⁷ Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
⁸ Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, QC, H3A 1A1, Canada. [email protected].
⁹ CHU Ste-Justine Research Center, Montreal, QC, H3T 1C5, Canada. [email protected].
¹⁰ Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada. [email protected].
¹¹ Department of Psychology, McGill University, Montreal, QC, H3G 1G1, Canada. [email protected].
¹² Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, H4B 1R6, Canada. [email protected].

Abstract

Purpose: The purpose of this study was to assess, in a large sample of healthy young adults, sex differences in the binding potential of [¹¹C]ABP688, a positron emission tomography (PET) tracer selective for the metabotropic glutamate type 5 (mGlu5) receptor.

Methods: High resolution [¹¹C]ABP688 PET scans were acquired in 74 healthy volunteers (25 male, 49 female, mean age 20 ± 3.0). Mean binding potential (BP_ND = f_ND * (B_avail / K_D)) values were calculated in the prefrontal cortex, striatum, and limbic regions using the simplified reference tissue model with cerebellar grey matter as the reference region.

Results: [¹¹C]ABP688 BP_ND was significantly higher in men compared to women in the prefrontal cortex (p < 0.01), striatum (p < 0.001), and hippocampus (p < 0.05). Whole-brain BP_ND was 17% higher in men. BP_ND was not related to menstrual phase in women.

Conclusions: Binding availability of mGlu5 receptors as measured by PET [¹¹C]ABP688 is higher in healthy men than women. This likely represents a source of variability in [¹¹C]ABP688 studies and could have relevance for sex differences in cognitive-behavioral functions and neuropsychiatric disorders.

Keywords: Gender; Metabotropic glutamate receptors; PET; mGluR5.

MeSH terms

Brain / diagnostic imaging
Brain / metabolism
Carbon Radioisotopes*
Female
Healthy Volunteers
Humans
Male
Oximes / metabolism*
Positron-Emission Tomography*
Protein Binding
Pyridines / metabolism*
Receptor, Metabotropic Glutamate 5 / metabolism*
Sex Characteristics*
Young Adult

Substances

3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
Carbon Radioisotopes
Carbon-11
Oximes
Pyridines
Receptor, Metabotropic Glutamate 5

Abstract

MeSH terms

Substances

Grants and funding