Integrated MRI and [11C]-PBR28 PET Imaging to Characterize In vivo Glial Activation in Amyotrophic and Primary Lateral Sclerosis: Cross Sectional and Longitudinal Study (P2.032)

Objective: Confirm our initial finding of increased [ 11 C]-PBR28 in the motor cortices of people with amyotrophic lateral sclerosis (ALS), study the longitudinal changes, and characterize the gray vs. white matter distribution of [ 11 C]-PBR28 uptake in a larger cohort of patients with ALS and extend our investigations to patients with primary lateral sclerosis (PLS). Background: There is a substantial unmet need to develop diagnostic and pharmacodynamic markers for ALS and PLS. [ 11 C]-PBR28 is a is a second-generation radioligand binds translocator protein 18 kDa (TSPO) to detect glial activation. Design/Methods: 53 ALS, 11 PLS and 21 healthy controls underwent brain imaging using an integrated PET-MR scanner. All individuals were genotyped for the Ala147Thr TSPO polymorphism and low affinity binders were excluded. Patients were clinically assessed using the upper motor neuron burden (UMNB), and the revised ALS functional rating scale (ALSFRS-R). [ 11 C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR), and compared between groups using voxel-wise, surface-based, and region of interest (ROI) analyses. Using MRI data, cortical thickness, and fractional anisotropy were compared between groups and correlated with the clinical data. [ 11 C]-PBR28 uptake and ALSFRS-R were compared longitudinally over six-month in ten ALS individuals. Results: Voxel wise, surface-based and ROI analyses revealed increased [ 11 C]-PBR28 uptake in the motor cortices in ALS participants compared to controls. This increase co-localized and correlated with decreased cortical thickness (r= − 0·49; P=0·0002), and reduced FA (r= − 0·56; p 11 C]-PBR28 signal correlated with higher UMNB (r= + 0·53, P 11 C]-PBR28 uptake was predominantly increased in the sub-cortical white matter of the motor cortices in the PLS group. [ 11 C]-PBR28 was stable over six-month in ten ALS individuals, although ALSFRS-R progressed at 0.5 points/month. Conclusions: [ 11 C]-PBR28 PET is a promising candidate molecular biomarker to measure the impact of experimental treatments on glial activation in future ALS clinical trials. Study Supported by: Harvard Neuro Discovery Center. The American Academy of Neurology, The Anne Young Fellowship award, The Spastic Paraplegia Foundation, and K23NS083715 from NINDS Disclosure: Dr. Alshikho has nothing to disclose. Dr. Zurcher has nothing to disclose. Dr. Loggia has nothing to disclose. Dr. Cernasov has nothing to disclose. Dr. Reynolds has nothing to disclose. Dr. Pijanowski has nothing to disclose. Dr. Chonde has nothing to disclose. Dr. Garcia has nothing to disclose. Dr. Mainero has nothing to disclose. Dr. Catana has nothing to disclose. Dr. Chan has nothing to disclose. Dr. Babu has nothing to disclose. Dr. Paganoni has nothing to disclose. Dr. Hooker has nothing to disclose. Dr. Atassi has nothing to disclose.