Related Experiment Video
Updated: May 24, 2026
Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
Published on: February 28, 2021
P2X 7-receptor binding in new-onset and secondary progressive MS - a [11C]SMW139 PET study
Jussi Lehto1,2,3, Richard Aarnio4, Jouni Tuisku4
1Turku PET Centre, Turku, Finland. juleht@utu.fi.
Background:
PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at 'smoldering' lesion rims have been implicated as drivers of disability progression. The P2X 7R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X 7R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.
Results:
Overall, tracer uptake in the MS brain was not significantly higher compared to HCs. In the 3 mm perilesional rim of all T1 lesions, tracer binding was higher among relapsing patients compared to progressive patients. Tracer binding was higher in males compared to females. Disease duration correlated with tracer binding in the normal appearing white matter. Age correlated negatively with tracer binding in the perilesional rims.
Conclusions:
Even as binding estimates obtained with the dual-input model were consistent with the expected distribution of P2X 7Rs in the MS brain, the small free fraction of the parent tracer may limit its accuracy and applicability, and binding estimates between subjects were highly variable. Conclusive evidence for the applicability of [11C]SMW139 to detect MS-related diffuse smoldering inflammation was not obtained.
Insights
Positron emission tomography (PET) imaging revealed no significant difference in P2X7 receptor binding in the MS brain compared to healthy controls. However, tracer binding varied by lesion proximity, patient sex, and disease duration.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Multiple Sclerosis (MS)
Background:
- Activated microglia, particularly at smoldering lesion rims, are implicated in MS disability progression.
- The P2X7 receptor (P2X7R) is upregulated on activated microglia.
- PET imaging offers a window into microglial activation in MS.
Purpose of the Study:
- To quantify P2X7R binding in the brains of progressive MS patients, relapsing MS patients, and healthy controls using a dual-input model.
- To investigate the relationship between P2X7R binding and MS pathology, including lesion proximity, disease duration, sex, and age.
Main Methods:
- Application of a single-tissue dual-input model for P2X7R quantification.
- PET imaging was performed on progressive MS patients, relapsing MS patients, and healthy controls.
- Analysis included normal-appearing white matter, perilesional areas, and thalamus.
Main Results:
- Overall tracer uptake in MS brains was not significantly higher than in healthy controls.
- Tracer binding was higher in the perilesional rim of T1 lesions in relapsing MS patients compared to progressive MS patients.
- Tracer binding was higher in males than females, and correlated with disease duration in normal-appearing white matter and negatively with age in perilesional rims.
Conclusions:
- While binding estimates aligned with expected P2X7R distribution, the parent tracer's small free fraction may affect accuracy and applicability.
- High variability in binding estimates between subjects was observed.
- Conclusive evidence for using [11C]SMW139 to detect diffuse smoldering inflammation in MS was not established.
