Tau imaging with [¹⁸ F]THK-5351 in progressive supranuclear palsy

Area of Science:

• Neuroimaging
• Neuropathology
• Radiochemistry

Background:

• Pathogenic protein aggregates, particularly tau, are key in neurodegenerative diseases like progressive supranuclear palsy (PSP).
• Accurate visualization of tau lesions is vital for understanding disease mechanisms and diagnosis.

Purpose of the Study:

• To evaluate a novel positron emission tomography (PET) tracer, [18F]THK-5351, for detecting tau lesions in living PSP patients.
• To assess the tracer's ability to map the regional distribution of tau pathology in the brain.

Main Methods:

• Autoradiography and immunohistochemistry on PSP brain sections using [3H]THK-5351.
• PET imaging with [18F]THK-5351 in nine healthy controls, 13 Alzheimer's disease patients, and three PSP patients.
• Amyloid-beta PET imaging using Pittsburgh compound B for comparison.

Main Results:

• [3H]THK-5351 demonstrated high selectivity for tau deposits in PSP brain sections.
• [18F]THK-5351 PET showed significantly higher retention in the globus pallidus and midbrain of PSP patients, not the temporal cortex.
• Amyloid imaging revealed no significant accumulation in the cerebral cortex of PSP patients.

Conclusions:

• [18F]THK-5351 PET imaging is a promising tool for visualizing tau lesions in PSP.
• This technique can aid in the differential diagnosis of tau protein-associated neurodegenerative disorders.