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 (a.k.a.[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. Though it is desirable to perform sufficient duration of a dynamic PET scan to estimate accurate non-displaceable binding potential (BPND), imaging over 1 hour is impractical for a clinical setting. This study was aimed at optimizing a protocol for a 20-min static emission scan to obtain a reliable target-to-reference ratio of radioligand concentrations in comparison with analytical models with dynamic scan data and 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 with a break between 60 and 90 min or 120 min 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 Serial arterial blood samples were withdrawn during the scan to determine a metabolite-corrected plasma input function.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 volume (VT) values was examined to estimate scan duration sufficient for robust determination of VT. BPND of [18F]PM-PBB3 was calculated using VT obtained with LGA with the cerebellum as a reference. An averaged target-to-cerebellum ratio in a 20-minute frame beginning at different time points after radioligand injection was calculated as standardized uptake value ratio (SUVR). SUVR-1 values were then compared with BPND to determine an optimal time frame to initiate the static scan. 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. All radiometabolites in plasma were polar than unmetabolized [18F]PM-PBB3. The parent fraction was decreased gradually to 20% at 60min and 9% at 150 min. 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 higher correlation with BPND than any other time frame. Conclusions[18F]PM-PBB3 showed reversible binding kinetics, which 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 the radioligand retention with sufficient robustness.Brain & Brain PET 2019に参加および発