title: Quantification of Tau Load Using [18F]AV1451 PET.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Model preference of [18F]AV1451 appears to depend on subject status and, in particular, VT. The relationship between model preference and VTsuggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_VBmodel. In addition, SRTM can be used to derive BPND.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands. s.golla@vumc.nl.
authors.forename: Sandeep S V
authors.initials: SSV
authors.lastname: Golla
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.|Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Timmers
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.|Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Colin
authors.initials: C
authors.lastname: Groot
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Verfaillie
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.|Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Anaesthesiology, VU University Medical center, Amsterdam, Netherlands.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schwarte
authors.affiliation: Avid Radiopharmaceuticals, Inc., Philadelphia, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.affiliation: Avid Radiopharmaceuticals, Inc., Philadelphia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Devous
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.|Department of Nuclear Medicine & Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.|Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Bart N M
authors.initials: BNM
authors.lastname: van Berckel
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D002243:Carbolines / Q000097:blood / Q000737:chemistry*; D016022:Case-Control Studies; D006801:Humans; D007700:Kinetics; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D002243:Carbolines; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
keywords: Alzheimer’s Disease; Flortaucipir; PET Pharmacokinetic Modeling; Tau Imaging; [18F]AV1451