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

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 (BP_ND) 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. BP_ND 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 BP_ND in the lateral prefrontal and anterior cingulate cortices. The lowest [¹¹C]ABP688 BP_ND 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 BP_ND 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.