Development, initial validation, and application of a visual read method for [¹⁸F]MK-6240 tau PET

Area of Science:

• Neuroimaging
• Radiopharmaceutical Development
• Alzheimer's Disease Diagnostics

Background:

• The [18F]MK-6240 positron emission tomography (PET) radiotracer targets neurofibrillary tangles (NFTs) in Alzheimer's disease (AD).
• It demonstrates high specificity, sensitivity, and low background signal in the brain.
• Clinical application requires a standardized visual assessment method for identifying and staging AD.

Purpose of the Study:

• To develop and validate a reproducible, clinically relevant visual read method for [18F]MK-6240 PET scans.
• To support the identification and staging of AD subjects compared to non-AD individuals and controls.

Main Methods:

• Five expert readers initially assessed 30 mixed-diagnosis scans, providing input on assessment features and clinical relevance.
• A four-class visual read classification system was defined based on reader input and scan characteristics.
• The method was validated through training two naïve readers, testing inter-rater agreement on 131 scans, and applying it to a diverse database of 1842 scans.

Main Results:

• A four-class visual read method was established: no uptake, medial temporal lobe (MTL) only, MTL and neocortical uptake, or uptake outside MTL.
• Excellent inter-rater reliability was achieved, with kappas of 1.0 for naïve readers and 0.98 for independent readers.
• All 1842 scans in the diverse database were successfully classified, with frequencies aligning with NFT histopathology literature.

Conclusions:

• The developed four-class visual read method for [18F]MK-6240 tau PET is trainable, reproducible, and clinically relevant.
• It accurately captures tau distribution patterns, including medial temporal, neocortical, and atypical patterns, supporting disease staging.
• This method facilitates the clinical use of [18F]MK-6240 PET for Alzheimer's disease assessment.