Quantification of Tau Load Using [18F]AV1451 PET.

Abstract

PURPOSE:

The tau tracer [18F]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 [18F]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 [18F]AV1451.

PROCEDURES:

Following intravenous injection of 225 ± 16 MBq [18F]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_VB) was the preferred model for all but one control. For AD patients, however, model preference shifted towards a reversible two tissue compartmental model (2T4k_VB). The simplified reference tissue model (SRTM) derived binding potential (BPND) 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 BPND (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 [18F]AV1451 appears to depend on subject status and, in particular, VT. The relationship between model preference and VT suggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_VB model. In addition, SRTM can be used to derive BPND.

• Authors: Sandeep S V Golla, Tessa Timmers, Rik Ossenkoppele, Colin Groot, Sander Verfaillie, Philip Scheltens, Wiesje M van der Flier, Lothar Schwarte, Mark A Mintun, Michael Devous, Robert C Schuit, Albert D Windhorst, Adriaan A Lammertsma, Ronald Boellaard, Bart N M van Berckel, Maqsood Yaqub
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 19 Issue 6 Pg. 963-971 (12 2017) ISSN: 1860-2002 [Electronic] United States
• PMID: 28374171 (Publication Type: Journal Article)

Chemical References

• Carbolines
• tau Proteins
• 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Topics

• Aged
• Alzheimer Disease (diagnostic imaging)
• Carbolines (blood, chemistry)
• Case-Control Studies
• Humans
• Kinetics
• Positron-Emission Tomography
• tau Proteins (metabolism)