The tracer 18F-AV-1451 may help diagnose progressive supranuclear palsy

Professor Chul Hyoung Lyoo
Yonsei University College of Medicine

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The tracer 18F-AV-1451 may help diagnose progressive supranuclear palsy

Yonsei researchers have identified a novel Korean-specific mutation that is expected to contribute in detecting and preventing relevant cancers.

Progressive supranuclear palsy (PSP) is an uncommon brain disorder that causes serious movement and balance problems. This condition involves abnormal accumulation of the tau protein in the brain, and its various clinical manifestations reflect the precise distribution of this accumulation.
Research into these distributions has been impeded by the lack of a tracer that selectively targets pathologic tau proteins in living patients, but the radioactive tracer 18F-AV-1451 has recently been shown to strongly bind pathologic tau proteins in patients with Alzheimer’s disease. A group of Yonsei University researchers, led by Prof. Chul Hyoung Lyoo, therefore decided “to investigate cortical and subcortical 18F-AV-1451 binding patterns in patients with PSP” using positron emission tomography (PET).

Prof. Lyoo’s team found that patients with PSP generally exhibited stronger 18F-AV-1451 binding than healthy control participants in the subcortical regions of the brain. Similar differences in 18F-AV-1451 binding were also observed between patients with PSP and those with Parkinson’s disease, which could be attributed to the abnormally weak 18F-AV-1451 binding in the substantia nigra, another region in the brain, in patients with Parkinson’s disease. The differences in 18F-AV-1451 binding in the globus pallidus could be used to distinguish patients with PSP from healthy controls and patients with Parkinson’s disease. Based on this, Prof. Lyoo’s team notes that “18F-AV-1451 PET may be useful for the differential diagnosis of PSP by aiming for highly increased pallidal uptake.”

Averaged 18F-AV-1451 PET images of three diagnostic groups
PSP patients show markedly increased 18F-AV-1451 binding in the globus pallidus and substantia nigra compared to healthy controls and patients with Parkinson’s disease.

However, unlike the differences in binding in the subcortical regions, there were no unusual 18F-AV-1451 binding patterns within the cortical regions in patients with PSP. The researchers also did not find any correlations between regional 18F-AV-1451 binding patterns and disease duration or severity, as measured based on either motor symptoms or mental state evaluations.
The lack of cortical binding or any correlation with disease severity suggests that 18F-AV-1451 PET “may be less than ideal for assessing tau pathology” in patients with PSP. The lack of cortical binding is particularly disappointing, as postmortem studies have shown that pathologic tau protein is found within the patients’ frontal and parietal cortices.
Nevertheless, this study has shown that 18F-AV-1451 has distinctive binding patterns within the brains of patients with PSP. Further research is needed to validate the clinical correlations of 18F-AV-1451 binding and the potential utility of 18F-AV-1451 PET in patients with PSP, but this study’s findings can serve as a starting point for such research.

Updated in Jan 2018

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Title of original article: Subcortical 18F-AV-1451 binding patterns in progressive supranuclear palsy
Journal: Movement Disorders
DOI: 10.1002/mds.26844
Contact corresponding author: Chul Hyoung Lyoo ( )