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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Aim
PET imaging with [18F]PM-PBB3 ([18F]APN-1607) has demonstrated the capability of this radioligand for high-contrast visualization of tau deposits in the brains of Alzheimer’s disease (AD) and diverse other neurodegenerative disorders. This study was aimed at determining an optimal time frame of a PET scan to obtain a reliable target-to-reference ratio of radioligand concentrations in comparison with analytical models with an arterial input function.
Methods
Ten subjects consisting of 5 healthy controls (HCs) and 3 AD and 2 progressive supranuclear palsy (PSP) patients underwent dynamic PET scans over 150 or 180 minutes after intravenous injection of [18F]PM-PBB3. Serial arterial blood samples were withdrawn during the scan to determine a metabolite-corrected plasma input function. Regional time-activity curves were analyzed with 1- and 2-tissue compartment models (TCMs) and Logan’s graphical analysis (LGA). Time-stability of total distribution (VT) values was examined to estimate scan duration sufficient for determination of VT. Non-displaceable biding potential (BPND) of [18F]PM-PBB3 was calculated using VT obtained with LGA, and SUVR in a 20-minute frame beginning at different time points after radioligand injection was calculated. SUVR-1 values were then compared with BPND to determine an optimal scan frame.
Results
A peak [18F]PM-PBB3 SUV in the brain approximated 2.5 at < 5 minutes, followed by rapid radioactivity washout. Radioligand retentions in the lateral temporal cortex of AD patients and midbrain of PSP patients were characteristically increased relative to HCs. Two-TCM better described the radioligand kinetics in target regions than 1-TCM. VT values obtained with LGA presented the highest time-stability, and SUVR-1 values at 90-110 min showed the highest correlation with BPND among different frames.
Conclusions
[18F]PM-PBB3 kinetics showed reversible binding and could be described without radiometabolite compartments in the brain. Estimation of SUVR at 90-110 min can be employed as a simplified means to quantify radioligand retention with sufficient robustness.
Establishment of a simplified method to quantify [18F]PM-PBB3 ([18F]APN-1607) binding in the brains of living human subjects
