Establishment of a simplified method to quantify [18F]PM-PBB3 ([18F]APN-1607) binding in the brains of living human subjects

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 Serial arterial blood samples were withdrawn during the scan to determine a metabolite-corrected plasma input function.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. ResultsA 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.13th Human Amyloid Imaging Conferenc