In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106

Area of Science:

• Neuroimaging
• Molecular Imaging
• Radiochemistry

Background:

• Neuroinflammation, characterized by microglial activation and translocator protein (TSPO) upregulation, is central to diseases like multiple sclerosis (MS).
• In vivo visualization of neuroinflammation remains challenging due to a lack of effective molecular imaging biomarkers.
• [18F]FEDAA1106 is a new positron emission tomography (PET) radioligand developed for quantifying TSPO in vivo.

Purpose of the Study:

• To investigate the diagnostic utility of the novel PET radioligand [18F]FEDAA1106 in patients with multiple sclerosis (MS).
• To assess the ability of [18F]FEDAA1106 to quantify TSPO expression and detect active lesions in the brains of MS patients.

Main Methods:

• Nine relapsing-remitting MS patients with active lesions and five healthy controls underwent dynamic PET scans with [18F]FEDAA1106.
• Quantitative analysis using kinetic modeling estimated binding potentials (BPND) and distribution volumes (VT).
• PET images were visually compared with MRI to identify radioligand uptake in MS lesions.

Main Results:

• No significant differences in BPND or VT values were observed between MS patients and healthy controls.
• Reliable quantification of BPND and VT in MS lesions was hindered by noisy time-activity curves.
• Visual assessment revealed minimal radioligand uptake in active MS lesions, with only one Gd-enhancing lesion showing uptake.

Conclusions:

• The PET radioligand [18F]FEDAA1106 did not effectively differentiate MS patients from controls or detect active MS brain lesions in this study.
• Future studies may benefit from stratifying participants based on genetics and TSPO binder status to potentially reveal differences.
• The diagnostic performance of [18F]FEDAA1106 for MS neuroinflammation requires further investigation with optimized methodologies.