TORONTO — Researchers at the University of Toronto presented a new PET imaging approach that quantifies synaptic loss in the spinal cord of multiple sclerosis patients at the 2026 Society of Nuclear Medicine and Molecular Imaging Annual Meeting. The technique, which measures synaptic density using SV2A PET imaging, offers a quantitative method to assess the brain’s functional wiring in living patients with the disease.
Multiple sclerosis affects millions of people worldwide and can cause physical disability, fatigue, and cognitive impairment. While traditionally viewed as a disease that damages the protective coating of nerves, it also involves loss of synapses—the connection points where brain cells communicate. Until now, in vivo quantification of synaptic density in the spinal cord had not been explored in multiple sclerosis.
The research team investigated SV2A PET imaging in both a mouse model of multiple sclerosis and in human patients. In mice with experimental autoimmune encephalomyelitis, a standard model of the disease, 18F-SynVesT-1 PET scans detected reductions in synaptic density within specific spinal cord regions, findings corroborated by binding studies.
In humans, the team performed 11C-UCB-J PET imaging on six multiple sclerosis patients and six healthy controls in collaboration with Yale University. Multiple sclerosis patients exhibited a 16.4 percent reduction in 11C-UCB-J binding across the brain compared to controls. Widespread reductions in binding were also observed in subcortical and spinal cord regions.
"This work represents an important step toward applying SV2A PET to quantify synaptic pathology in multiple sclerosis across preclinical and human studies," said Chao Zheng, PhD, senior author and principal investigator of the study, based at the Centre for Addiction and Mental Health and the University of Toronto. "Our team demonstrated that SV2A PET can detect spinal cord synaptic loss in a mouse model of multiple sclerosis and led the translational framework linking these findings to pilot human multiple sclerosis PET imaging. Together, these cross-species data support SV2A PET as a quantitative tool for monitoring synaptic pathology and evaluating future therapeutic strategies."
Pou Hong Justin Chia, a graduate student at the Centre for Addiction and Mental Health and lead presenter of the study, said the research provides direct evidence in living subjects that synaptic loss is a widespread feature of multiple sclerosis. "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," Chia said.
SV2A PET imaging in multiple sclerosis is currently available for clinical trials at specialized academic centers but is not yet part of standard clinical care. Data from this pilot study is a necessary step toward larger clinical trials, and if validated in broader studies, the approach could be integrated into clinical practice and drug development over the next several years.