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

Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):152-162. doi: 10.1007/s00259-015-3167-6. Epub 2015 Aug 21.

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 [(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.

Keywords: Healthy controls; Metabotropic glutamate receptor 5; Positron emission tomography; [11C]ABP688.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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