Imaging Proinflammatory Microglia in Parkinson Disease Using [¹¹C]SMW139 PET: A Multicenter Study.

Area of Science:

• Neuroscience
• Radiology
• Immunology

Background:

• Translocator protein (TSPO) PET studies indicate increased glial cell density in Parkinson disease (PD).
• TSPO tracers cannot distinguish between pro-inflammatory and anti-inflammatory processes, hindering therapeutic development.
• P2X7 receptor is expressed on pro-inflammatory microglia, making it a potential target for PD research.

Purpose of the Study:

• To investigate pro-inflammatory signals in PD using [11C]SMW139 PET targeting the P2X7 receptor.
• To assess differences in P2X7 receptor binding between PD patients and healthy controls.
• To explore associations between P2X7 receptor binding and PD symptom severity or disease duration.

Main Methods:

• A multicenter study included 15 PD patients and 15 healthy controls (HCs).
• Participants underwent a 90-minute [11C]SMW139 PET scan with continuous blood sampling.
• Quantification of [11C]SMW139 used a 2-tissue compartment model; the distribution volume of the parent (V_Tp) was the primary parameter.

Main Results:

• PD patients exhibited significantly higher [11C]SMW139 V_Tp in the putamen and whole cortex compared to HCs.
• Exploratory analysis revealed higher V_Tp in the orbitofrontal cortex of PD patients.
• No significant association was found between V_Tp and motor symptom severity or disease duration in PD patients.

Conclusions:

• [11C]SMW139 PET demonstrated increased P2X7 receptor binding in the putamen and brain cortex of PD patients.
• This suggests elevated levels of pro-inflammatory microglia in these brain regions in PD.
• Targeting P2X7 receptors may offer a novel therapeutic or diagnostic approach for PD.