Journal Article

Quantification of Tau Load Using 18FAV1451 PET

Windhorst, Albert D., Golla, Sandeep S. V., van Berckel, Bart N. M., Ossenkoppele, Rik, Devous, Michael, van der Flier, Wiesje M., Mintun, Mark A., Verfaillie, Sander, Schwarte, Lothar, Yaqub, Maqsood, Groot, Colin, Lammertsma, Adriaan A., Boellaard, Ronald, Timmers, Tessa, Schuit, Robert C., Scheltens, Philip

2017

Overview

Purpose The tau tracer [ 18 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 [ 18 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 [ 18 F]AV1451. Procedures Following intravenous injection of 225 ± 16 MBq [ 18 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 B ) 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 B ). The simplified reference tissue model (SRTM) derived binding potential (BP ND ) showed good correlation (AD: r 2  = 0.87, slope = 1.06; controls: r 2  = 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 2  = 0.93, slope = 1.07) and SRTM-derived BP ND ( r 2  = 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 [ 18 F]AV1451 appears to depend on subject status and, in particular, V T . The relationship between model preference and V T suggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_V B model. In addition, SRTM can be used to derive BP ND .

• Publisher: Springer US,Springer Nature B.V
• Subject: Aged / Alzheimer Disease - diagnostic imaging / Alzheimer's disease / Binding / Biomarkers / Carbolines - blood / Carbolines - chemistry / Case-Control Studies / Correlation analysis / Humans / Imaging / Intravenous administration / Kinetics / Longitudinal studies / Medicine / Medicine & Public Health / Neurodegenerative diseases / Patients / Pharmacology / Positron emission / Positron-Emission Tomography / Radiology / Research Article / Tau protein / tau Proteins - metabolism / Tomography