Abstract
1057
Objectives: To compare and contrast the expression of metabotropic glutamate receptor subtype 5 (mGluR5) in the living brains of participants with autism spectrum disorder (ASD), fragile X syndrome (FXS), and typical development (TD).
Methods: Investigators at the Institute for Neurodegenerative Disorders (IND), New Haven, Connecticut, and the Johns Hopkins University (JHU), Baltimore, Maryland, independently administered positron emission tomography (PET) after the intravenous bolus injection of 185 megabecquerels (MBq) [5 millicuries (mCi)] of 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB) to participants with ASD (N=7, age 19.71+2.06), FXS (N=9, age 26.67+4.24), and TD (N=18, age 33.72+14.04). PET was conducted at IND on an ECAT EXACT HR+ PET for 90-120 min after injection and at JHU on a high resolution research tomograph (HRRT) for 0-90 min after injection. PET data for participants from IND were represented as the standard uptake value ratio (SUVR) with the whole cerebellum as reference region and from JHU were estimated as regional nondisplaceable binding potentials (BPNDs) by reference tissue graphical analysis (RTGA) with the cerebellar white matter as the reference region. Assuming that there is no difference in nonspecific tracer binding among regions and among participant cohorts, we approximated BPNDs for participants from IND by (SUVR-1). Due to the small sample size we expressed the results as dot plots with box plots representing descriptive statistics. The findings were represented for the cohorts of participants with ASD, FXS, and TD. For each cohort (ASD, FXS, and TD) participants from IND and JHU were grouped together. Male and female participants were represented by different colors.
Results: Although mean mGluR5 uptake was ordered FXS < ASD < TD for the posterior cingulate gyrus (Image 1) and the parietal (Image 2), occipital (Image 3), and temporal (Image 4) lobes, the mGluR5 uptake for participants with FXS < the equivalent values of TD and ASD for the thalamus (Th) (Image 5) and the striatum. Limitations: Variability in age (ASD < FXS < TD), basal metabolic index (BMI) (ASD < TD < FXS), scanner, scan times, and scan analyses confound the interpretation of the findings. Participants with ASD were younger than other participants. Some participants with TD were older than participants with ASD and FXS. The density of mGluR5s may decrease with age so the [18F]FPEB values of TD < ASD may reflect the reductions in receptors related to age. Participants with ASD and TD included men and women while only men with FXS were studied. The effects of sex may confound comparisons and contrasts among the cohorts.
Conclusions: Our prior report that the cerebral expression of mGluR5s is lower in all brain regions of men with FXS than men with TD (Brašić, et al., Brain Sci, 2020, 10, 988, https://doi.org/10.3390/brainsci10120899) was confirmed in larger cohorts of individuals of both sexes with FXS and TD . Confirmation in other cohorts in other locations is needed for (A) the variable mGluR5 expression in different brain regions of participants with ASD and (B) the pattern of higher mGluR5 expression in ASD than TD in cortical areas and equivalent mGluR5 expression in ASD and TD in subcortical regions. These results indicate that this protocol may be a valuable tool to measure mGluR5 expression in the living brains of participants with ASD and FXS for clinical trials and other investigations. Funding: Radiology BRidge/Development Funding Initiative to STimulate and Advance Research (RAD BriteStar Bridge) Award from the Johns Hopkins University School of Medicine to JRB; the Intellectual & Developmental Disabilities Research Center (U54 HD079123), Kennedy Krieger Institute to JRB; and the Johns Hopkins Institute for Clinical and Translational Research (ICTR) (UL1 TR003098) to JRB.
