A new method to quantify tau pathologies with (11)C-PBB3 PET using reference tissue voxels extracted from brain...

Area of Science:

• Neuroimaging
• Nuclear Medicine
• Radiochemistry

Background:

• Quantitative in vivo imaging of tau pathologies is crucial for diagnosing neurodegenerative tauopathies and evaluating tau-targeting drugs.
• Traditional reference tissue models for tau positron emission tomography (PET) rely on regions devoid of tau binding, often the cerebellar cortex.
• However, tau accumulation in the cerebellum in certain tauopathies (e.g., progressive supranuclear palsy, corticobasal degeneration) limits the utility of this reference region.

Purpose of the Study:

• To develop and validate a novel method for quantifying specific binding of the tau PET radioligand (11)C-PBB3.
• To utilize reference voxels from cortical gray matter, which exhibit low likelihood of tau accumulation, as an alternative to cerebellar reference regions.
• To enable accurate tau quantification across diverse tauopathies, including those with cerebellar tau deposition.

Main Methods:

• Reanalyzed (11)C-PBB3 PET data from mild Alzheimer's disease patients and healthy controls.
• Generated binding potential parametric images using standard cerebellar reference tissue.
• Developed a histogram-based approach to identify low-binding cortical gray matter voxels as reference regions for new parametric image generation.

Main Results:

• Reference tissue voxels identified via histogram analysis were distributed throughout the cortical gray matter in both patient and control groups.
• The new method demonstrated a strong correlation (r² = 0.94) with the standard cerebellar reference method for estimating binding potential.
• Binding estimates using the novel cortical reference method were slightly higher (~0.14) than those from the standard cerebellar method.

Conclusions:

• A novel, validated method for quantifying tau lesions using cortical gray matter as a reference region has been developed.
• This approach effectively quantifies tau deposits even when tau pathology affects the cerebellum and other extensive brain areas.
• The method shows promise for application to all tauopathy subtypes and various tau PET ligands beyond (11)C-PBB3.