Reference Tissue-Based Kinetic Evaluation of 18F-AV-1451 for Tau Imaging.

Area of Science:

• Neuroimaging
• Radiochemistry
• Nuclear Medicine

Background:

• Alzheimer disease (AD) is characterized by tau pathology.
• Tau-specific positron emission tomography (PET) radioligands are crucial for in vivo imaging.
• 18F-AV-1451 is a novel tau PET tracer requiring kinetic evaluation.

Purpose of the Study:

• To evaluate the in vivo kinetics of 18F-AV-1451 in cognitively healthy controls (HC) and AD subjects.
• To compare different kinetic modeling methods for 18F-AV-1451 quantification.
• To determine optimal imaging time windows for standardized uptake value ratios (SUVRs).

Main Methods:

• 18F-AV-1451 PET imaging was performed on 43 subjects (5 young HCs, 23 older HCs, 15 AD subjects) with data collected from 0-150 min post-injection.
• Nondisplaceable binding potentials (BPND) were calculated using simplified reference tissue model (SRTM) and SRTM2; Logan graphical analysis distribution volume ratio (DVR) was calculated for 30-150 min (DVR30-150).
• Pearson correlations compared reference standards (SRTM, SRTM2, DVR30-150) to 20-min SUVRs across various time intervals and binding levels (low/high ROIs).

Main Results:

• SRTM2 BPND+1 and DVR30-150 showed good agreement, with nonlinear relationships compared to SRTM BPND+1 in high binding regions (hROIs).
• SUVRs in hROIs increased over time, with the 120-140 min interval showing the highest correlation with reference standards for hROIs.
• Optimal SUVR time intervals varied by binding level, with 80-100 min identified as a compromise for both low and high binding regions.

Conclusions:

• SUVR80-100 provides a reasonable compromise for quantifying 18F-AV-1451 binding in both low and high binding regions.
• The lack of a plateau in hROIs emphasizes the need for precise timing in longitudinal studies.
• Kinetic modeling and optimal SUVR windows are essential for accurate 18F-AV-1451 quantification in AD research.