TY - JOUR
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
N1 - Funding Information:
Acknowledgements. This research was supported by AVID Radiopharmaceuticals, ZonMw, the European Union’s Seventh Framework Programme (FP7/2007-2013), grant agreement no. HEALTH-F2-2011-278850 (INMiND), the Marie Curie FP7 International Outgoing Fellowship [628812] (to R.O.) and the donors of [Alzheimer’s Disease Research], a program of BrightFocus Foundation (to R.O.).
Publisher Copyright:
© 2017, The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
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.
AB - 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.
KW - Alzheimer’s Disease
KW - Flortaucipir
KW - PET Pharmacokinetic Modeling
KW - Tau Imaging
KW - [F]AV1451
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U2 - 10.1007/s11307-017-1080-z
DO - 10.1007/s11307-017-1080-z
M3 - Article
C2 - 28374171
AN - SCOPUS:85017017876
SN - 1536-1632
VL - 19
SP - 963
EP - 971
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -