Investigating Metabotropic Glutamate Receptor 5 (mGluR5) in Autism Spectrum Disorder with [18F]FPEB PET Imaging
Faranak Ebrahimian Sadabad1, Yanghong Yang1, Paul Gravel1, Adam Naples2, Kristen Torres1, Nabeel Nabulsi1, Jim Ropchan1, Yiyun Huang1, Ansell Hillmer1, Irina Esterlis3, Richard Carson1, James Mcpartland2, David Matuskey1
1Radiology and Biomedical Imaging, Yale University, 2Child Study Center, Yale University, 3Department of Psychiatry, Yale University, Yale University
Objective:
We aim to quantify mGluR5 availability in autistic adults using the specific binding PET tracer [18F]FPEB.
Background:
The neural basis of autism spectrum disorder (ASD) is poorly understood at the molecular level. Evidence from animal models, genetics, post-mortem studies, and single-gene disorders suggests a possible involvement of metabotropic glutamate receptor 5 (mGluR5). 
Design/Methods:

Sixteen autistic individuals (mean age ±SD: 25.93± 4.69, 11 males, 5 females), and sixteen demographically matched neurotypical (NT) individuals (mean age ±SD:28.43 ± 3.31, 11 males, 5 females) were scanned using a positron emission tomography (PET) high-resolution research tomograph (HRRT). Volume of distribution (VT: ratio of activity in tissue relative to blood) was the primary outcome measure and computed with equilibrium analysis using a venous input function. Brain regions were delineated with a defined anatomic template applied to subjects' structural MR scans. Partial volume corrections were applied to control for possible volumetric differences. T-tests were calculated for between-group differences, and p-values were uncorrected for multiple comparisons, given the exploratory nature of this work.

Results:

We observed significantly lower mGluR5 availability in all regions, that varied from ‑16% to -23% in ASD compared to NT. This was lowest in the left frontal pole ( -23%, p=0.003) and left cingulate (-23%, p=0.003) and included important areas such as the frontal lobe (-19%, p=0.01), temporal lobe (-19%, p=0.01), cerebellum (-19%, p<0.01) and fusiform gyrus (-18%, p=0.02).

Conclusions:

This in vivo investigation with mGluR5 PET in people with ASD is the largest sample to date (to our knowledge) and found robust preliminary evidence of lower mGluR5 availability compared to NT.

10.1212/WNL.0000000000206171