A new PET imaging approach that measures synaptic density in the spinal cord provides a quantitative way to assess the brain's functional wiring in patients with multiple sclerosis. With this personalized information, physicians can monitor disease progression and evaluate whether new treatments are working to protect or restore these critical connections.
 
MS is a condition that affects millions of people worldwide and can cause physical disability, fatigue, and cognitive impairment. While MS 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.
 
In the study, researchers at the Centre for Addiction and Mental Health at the University of Toronto conducted 18F-SynVesT-1 PET scans in mice with experimental autoimmune encephalomyelitis, a mouse model of MS, 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. To provide a translational context, 11C-UCB-J PET imaging was performed on six MS patients and six healthy controls in collaboration with Yale University. Total volume of distribution maps were generated and human PET data were compared.
 
In the MS-model mice, 18F-SynVesT-1 PET successfully detected significant reductions in synaptic density within specific regions of the spinal cord, which were corroborated by binding studies. In the human PET study, MS patients exhibited a 16.4 percent reduction in 11C-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 model.
 
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers said this work represents an important step toward applying SV2A PET to quantify synaptic pathology in MS across preclinical and human studies, and provides direct evidence in living subjects that synaptic loss is a widespread feature of MS.
 
A positron emission tomography scan is an imaging test that creates images of organs and tissues at work. Using a safe, injectable radioactive chemical called a radiotracer and a device called a PET scanner, the scanner detects cells that absorb large amounts of the radiotracer, which indicates a potential health problem. Currently, SV2A PET imaging in MS is available for clinical trials at specialized academic centers. While it is not yet a routine part of standard clinical care, the researchers note that data from this pilot study is a necessary step toward larger clinical trials. If validated in larger studies, this imaging approach could be integrated into clinical practice and drug development during the next several years.
 
The findings were presented at the Society of Nuclear Medicine and Molecular Imaging's 2026 Annual Meeting.