量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Background:
We recently developed a novel fluorinated tau PET ligand, [18F]PM-PBB3, to improve characteristics of [11C]PBB3. Our preclinical evidence suggested that [18F]PM-PBB3 could capture tau deposits in living brains with high contrast and favorable kinetics. Here, we conducted a head-to-head comparison between PET data obtained using [11C]PBB3 and [18F]PM-PBB3 in patients with Alzheimer’s disease (AD) and non-AD tauopathy.
Methods:
Patients with AD and progressive supranuclear palsy (PSP), and healthy controls (HCs) underwent three PET scans with [11C]PiB, [11C]PBB3, and [18F]PM-PBB3. In the scan with [18F]PM-PBB3, arterial blood sampling was performed to determine binding potential (BPND) of the radioligand based on a compartment model. We also calculated BPND by a reference tissue model and standardized uptake value ratio (SUVR) using the cerebellum gray matter as reference. These estimates were compared to SUVR values of [11C]PBB3 in each subject.
Results:
The BPND values of [18F]PM-PBB3 by a reference tissue model and SUVR were in good agreement with those by a compartment model. Compared to [11C]PBB3, the peak brain radioactivity and contrast for tau lesions yielded by [18F]PM-PBB3 were almost double of those produced by [11C]PBB3. Unlike [11C]PBB3, [18F]PM-PBB3 showed minimal off-site binding in the brain parenchyma including the striatum. Binding of [18F]PM-PBB3 in the brainstem was not evident in AD patients and HCs, but was prominent in PSP patients, resulting in a vivid contrast between PSP patients and the other subjects.
Conclusion:
The current results indicate that [18F]PM-PBB3 would be a promising PET ligand to quantify tau accumulation in AD and PSP patients with suitable kinetics and high contrast. The wide dynamic range and minimal parenchymal off-site binding of [18F]PM-PBB3 would allow its application to differentiations among AD, non-AD tauopathies and HC by both visual inspection and quantitative assessments on an individual basis in a clinical workup.
A head-to-head comparison between [11C]PBB3 and [18F]PM-PBB3 in patients with AD and non-AD tauopathy
