SNMMI: PET reveals new brain activity in multiple sclerosis

LOS ANGELES -- PET imaging provides evidence that a loss of brain synapses is a widespread feature of multiple sclerosis, according to a study presented June 2 at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting. 

A team at the University of Toronto demonstrated that radiotracers that bind to a protein on synapses called synaptic vesicle glycoprotein 2A (SV2A) can visualize and quantify synaptic density loss in the spinal cord, first in a mouse model and then in humans, noted graduate student Pou Hong Justin Chia. 

“Together, these cross-species data support SV2A PET as a quantitative tool for monitoring synaptic pathology and evaluating future therapeutic strategies,” Chia said.

Representative SV2A PET images comparing synaptic density in healthy and disease states. The left panel shows F-18 SynVesT-1 PET distribution volume (VT) maps of the brain and spinal cord in a naïve control mouse and a mouse with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. The right panel shows Cu-11 UCB-J PET images of the brain of a 46-year-old male healthy control (left) and 43-year-old female MS patient (right).Pou Hong Justin Chia and SNMMI

Multiple sclerosis is a condition that affects millions of people worldwide and can cause physical disability, fatigue, and cognitive impairment. While multiple sclerosis is traditionally viewed as a disease that damages the protective coating of nerves, there is also another, more subtle type of damage: the loss of synapses, which are the vital connection points where brain cells communicate, Chia and colleagues explained. 

To elucidate the connection, the researchers first analyzed F-18 SynVesT-1 PET scans in mice with experimental autoimmune encephalomyelitis, a widely used mouse model of multiple sclerosis, and in healthy control mice. Spinal cord regions of interest were defined, and total volume of distribution and radiotracer binding were quantified and compared between groups. The scans successfully detected significant reductions in synaptic density and were corroborated by the binding studies. 

Next, in collaboration with researchers at Yale University in New Haven, CT, the researchers used a tracer called carbon-11 (C-11) UCB-J -- which like F-18 SynVesT-1 binds to SV2A -- and performed PET imaging on six multiple sclerosis patients and six healthy controls. The patients exhibited a 16.4% reduction in C-11 UCB-J binding across the brain as compared to healthy controls. Widespread reductions were also observed in subcortical and spinal cord regions, mirroring the extensive synaptic pathology seen in the preclinical mouse model. 

“This work represents an important step toward applying SV2A PET to quantify synaptic pathology in multiple sclerosis across preclinical and human studies,” added Chao Zheng, PhD, senior author and principal investigator of the study. 

Understanding how and where these connections are lost can help explain the symptoms patients experience and give doctors and researchers a more sensitive way to detect disease-related changes, monitor progression over time, and better understand how multiple sclerosis and other neurological diseases affect the brain and spinal cord, according to the group. 

“If validated in larger studies, this imaging approach could be integrated into clinical practice and drug development over the next several years,” the researchers concluded. 

Check out AuntMinnie’s full coverage of SNMMI 2026 on our ShowCast.