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Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [11C]ABP688 PET

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Abstract

Purpose

Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [11C]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 [11C]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 [11C]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 [11C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [11C]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 [11C]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.

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Compliance with Ethical Standards

Funding

The study was funded by the Savoy Foundation for Epilepsy (www.savoy-foundation.ca) (pilot project grant to EK and PRN and PhD studentship to JMD), and partially by the American Epilepsy Society (www.aesnet.org) (Early Career Physician Scientist Award to EK), Canadian Institutes of Health Research (CIHR) (www.cihr-irsc.gc.ca) [MOP-115131 to PRN and MOP-93614 to EK], and the Fonds de la recherche en santé du Québec (www.frqs.gouv.qc.ca) (PRN, research fellow).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Montreal Neurological Institute Research Ethics Board and the institutional review board of McGill University, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room 786, Montreal, Quebec, H3A 2B4, Canada

    Jonathan M. DuBois, Manuel Porras-Betancourt, Gassan Massarweh, Jean-Paul Soucy, Pedro Rosa-Neto & Eliane Kobayashi

  2. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA

    Olivier G. Rousset

  3. Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Canada

    Jared Rowley & Pedro Rosa-Neto

  4. PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada

    Andrew J. Reader

  5. Division of Imaging Sciences and Biomedical Engineering, King’s College London, St. Thomas’ Hospital, London, UK

    Andrew J. Reader

  6. Department of Epidemiology, Biostatistics and Occupational health, McGill University, Montreal, Canada

    Aurelie Labbe

  7. Department of Psychiatry, Douglas Mental Health University Institute / Douglas Institut Universitaire en Santé Mentale, Montreal, Canada

    Aurelie Labbe

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  1. Jonathan M. DuBois
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Correspondence to Jonathan M. DuBois or Eliane Kobayashi.

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Online Resource 1

Simplified representation of volume-to-surface sampling method. (a) Left hemisphere shown in the coronal plane of a single subject’s T1 MRI. (b) Enlarged view of the anterior portion of the temporal lobe. A white line denotes the white matter surface and a blue line denotes the pial surface. An RBV-PVC BPND image (in yellow-red color scale) is co-registered and superimposed over the T1 MRI. The black dotted line represents corresponding vertices, with the midpoint indicated by the black circular point. In this example, BPND values are sampled from the midpoint to the surface mesh. The vertex corresponding to the midpoint is denoted by the green circle on the magnified surface mesh (c). The smaller white box denotes the region of the anterior temporal lobe that the magnified surface mesh corresponds to. RBV-PVC BPND values for all vertices are shown on the lateral left hemisphere pial surface of the same subject (d). (GIF 464 kb)

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DuBois, J.M., Rousset, O.G., Rowley, J. et al. Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [11C]ABP688 PET. Eur J Nucl Med Mol Imaging 43, 152–162 (2016). https://doi.org/10.1007/s00259-015-3167-6

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