Comparing and combining TSPO-PET tracers in tauopathies

Area of Science:

• Neuroscience
• Radiology
• Biomedical Imaging

Background:

• Neuroinflammation, driven by microgliosis, is central to neurodegenerative diseases like Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP).
• Positron Emission Tomography (PET) imaging targeting the translocator protein (TSPO) allows in vivo assessment of microgliosis.
• Existing TSPO tracers show consistent disease-specific patterns, but direct quantitative comparisons across different tracers in tauopathies are lacking.

Purpose of the Study:

• To apply and evaluate a TSPO-PET standardization pipeline for harmonizing multi-center data.
• To quantitatively compare and combine TSPO-PET data from clinically matched AD and PSP cohorts.
• To assess the comparability of different TSPO-PET tracers ([¹¹C]PK11195, [¹⁸F]GE-180, [¹¹C]PBR28) in neurodegenerative diseases.

Main Methods:

• Patients with PSP and AD, along with control participants, underwent PET scans using [¹¹C]PK11195, [¹⁸F]GE-180, or [¹¹C]PBR28 across multiple centers.
• A standardized pre-processing pipeline was implemented, and standardized uptake volume ratio (SUVR) values were z-scored using tracer-specific control data.
• Dissimilarity analyses were performed to assess tracer differences across clinically matched cohorts.

Main Results:

• In PSP cohorts, [¹¹C]PK11195 and [¹⁸F]GE-180 binding patterns were comparable after standardization.
• In AD cohorts, tracer comparability was less consistent: [¹¹C]PK11195 and [¹⁸F]GE-180 showed the highest comparability, followed by [¹⁸F]GE-180 vs. [¹¹C]PBR28, and then [¹¹C]PK11195 vs. [¹¹C]PBR28.
• The standardization pipeline demonstrated effectiveness in harmonizing TSPO-PET tracers for neuroinflammation quantification in PSP.

Conclusions:

• The developed pipeline successfully harmonized TSPO-PET tracers for standardized neuroinflammation quantification in PSP cohorts.
• The standardization pipeline's effectiveness was less robust when applied to Alzheimer's disease cohorts.
• Further refinement may be needed to achieve robust cross-tracer comparability in AD using TSPO-PET imaging.