Quantification of Tau Load Using [18F]AV1451 PET

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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: r2 = 0.87, slope = 1.06; controls: r2 = 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 (r2 = 0.93, slope = 1.07) and SRTM-derived BPND (r2 = 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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular Imaging and Biology
DOIs
StateAccepted/In press - Apr 3 2017

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Alzheimer Disease
Intravenous Injections
Positron-Emission Tomography
Longitudinal Studies
Software
Pharmacokinetics
Biomarkers
Ligands

Keywords

  • Alzheimer’s Disease
  • Flortaucipir
  • PET Pharmacokinetic Modeling
  • Tau Imaging
  • [F]AV1451

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Golla, S. S. V., Timmers, T., Ossenkoppele, R., Groot, C., Verfaillie, S., Scheltens, P., ... Yaqub, M. (Accepted/In press). Quantification of Tau Load Using [18F]AV1451 PET. Molecular Imaging and Biology, 1-9. https://doi.org/10.1007/s11307-017-1080-z

Quantification of Tau Load Using [18F]AV1451 PET. / Golla, Sandeep S V; Timmers, Tessa; Ossenkoppele, Rik; Groot, Colin; Verfaillie, Sander; Scheltens, Philip; van der Flier, Wiesje M.; Schwarte, Lothar; Mintun, Mark A.; Devous, Michael; Schuit, Robert C.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Boellaard, Ronald; van Berckel, Bart N M; Yaqub, Maqsood.

In: Molecular Imaging and Biology, 03.04.2017, p. 1-9.

Research output: Contribution to journalArticle

Golla, SSV, Timmers, T, Ossenkoppele, R, Groot, C, Verfaillie, S, Scheltens, P, van der Flier, WM, Schwarte, L, Mintun, MA, Devous, M, Schuit, RC, Windhorst, AD, Lammertsma, AA, Boellaard, R, van Berckel, BNM & Yaqub, M 2017, 'Quantification of Tau Load Using [18F]AV1451 PET', Molecular Imaging and Biology, pp. 1-9. https://doi.org/10.1007/s11307-017-1080-z
Golla SSV, Timmers T, Ossenkoppele R, Groot C, Verfaillie S, Scheltens P et al. Quantification of Tau Load Using [18F]AV1451 PET. Molecular Imaging and Biology. 2017 Apr 3;1-9. https://doi.org/10.1007/s11307-017-1080-z
Golla, Sandeep S V ; Timmers, Tessa ; Ossenkoppele, Rik ; Groot, Colin ; Verfaillie, Sander ; Scheltens, Philip ; van der Flier, Wiesje M. ; Schwarte, Lothar ; Mintun, Mark A. ; Devous, Michael ; Schuit, Robert C. ; Windhorst, Albert D. ; Lammertsma, Adriaan A. ; Boellaard, Ronald ; van Berckel, Bart N M ; Yaqub, Maqsood. / Quantification of Tau Load Using [18F]AV1451 PET. In: Molecular Imaging and Biology. 2017 ; pp. 1-9.
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T1 - Quantification of Tau Load Using [18F]AV1451 PET

AU - Golla, Sandeep S V

AU - Timmers, Tessa

AU - Ossenkoppele, Rik

AU - Groot, Colin

AU - Verfaillie, Sander

AU - Scheltens, Philip

AU - van der Flier, Wiesje M.

AU - Schwarte, Lothar

AU - Mintun, Mark A.

AU - Devous, Michael

AU - Schuit, Robert C.

AU - Windhorst, Albert D.

AU - Lammertsma, Adriaan A.

AU - Boellaard, Ronald

AU - van Berckel, Bart N M

AU - Yaqub, Maqsood

PY - 2017/4/3

Y1 - 2017/4/3

N2 - 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: r2 = 0.87, slope = 1.06; controls: r2 = 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 (r2 = 0.93, slope = 1.07) and SRTM-derived BPND (r2 = 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.

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