¹¹C-PBR28 and ¹⁸F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis

Area of Science:

• Neuroscience
• Radiology
• Immunology

Background:

• Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
• Microglial activation is a key pathological feature in MS, contributing to neuroinflammation and neurodegeneration.
• Translocator protein (TSPO) is a marker of neuroinflammation, often upregulated in activated microglia.

Purpose of the Study:

• To assess microglial activation in lesions and normal-appearing white matter (NAWM) in MS patients using Positron Emission Tomography (PET).
• To investigate the relationship between TSPO availability and different lesion types in MS.
• To compare TSPO binding in MS patients with healthy volunteers.

Main Methods:

• Thirty-four MS patients (7 SPMS, 27 RRMS) and 30 healthy volunteers underwent PET scanning.
• TSPO radioligands (11C-PBR28 or 18F-PBR111) were used to measure regional TSPO availability (distribution volume ratio, DVR).
• White matter lesions (WMLs) were classified based on DVR patterns: active, peripherally active, inactive, or undifferentiated.

Main Results:

• Mean TSPO DVR in NAWM was significantly higher in MS patients than in healthy controls for both radioligands.
• WMLs exhibited heterogeneous TSPO uptake patterns, but individual WML DVR strongly correlated with individual patient NAWM DVR.
• Active lesions were detected in all MS patients, including those on advanced treatments, with a higher proportion of inactive lesions in SPMS compared to RRMS.

Conclusions:

• TSPO radioligand uptake is elevated in the brains of MS patients, indicating increased neuroinflammation.
• WMLs in MS display diverse patterns of TSPO binding, suggesting varied inflammatory states.
• The presence of active lesions across all MS subtypes warrants further investigation into their prognostic significance.