Quantification of Tau Load Using [F]AV1451 PET.

Purpose: The tau tracer [F]AV1451, also known as flortaucipir, is a promising ligand for imaging tau accumulation in Alzheimer's disease (AD). Most of the previous studies have quantified tau load using standardized uptake value ratios (SUVr) derived from a static [F]AV1451 scan. SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [F]AV1451.

Procedures: Following intravenous injection of 225 ± 16 MBq [F]AV1451, 130 min dynamic PET scans were performed in five biomarker confirmed AD patients and five controls. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function. Next, regional time-activity curves were generated using PVElab software. These curves were analysed using several pharmacokinetic models.

Results: The reversible single tissue compartment model (1T2k_V) was the preferred model for all but one control. For AD patients, however, model preference shifted towards a reversible two tissue compartmental model (2T4k_V). The simplified reference tissue model (SRTM) derived binding potential (BP) showed good correlation (AD: r  = 0.87, slope = 1.06; controls: r  = 0.87, slope = 0.86) with indirect plasma input binding (distribution volume ratio-1). Standardized uptake value ratios (80-100 min) correlated well with DVR (r  = 0.93, slope = 1.07) and SRTM-derived BP (r  = 0.84, slope = 0.95). In addition, regional differences in tracer binding between subject groups in different tau-specific regions were observed.

Conclusions: Model preference of [F]AV1451 appears to depend on subject status and, in particular, V. The relationship between model preference and V suggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_V model. In addition, SRTM can be used to derive BP.