title: Tracer Kinetic Analysis of (S)-¹⁸F-THK5117 as a PET Tracer for Assessing Tau Pathology.
abstract: Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-(18)F-THK5117.
  
  
  METHODS
  Nine subjects (5 with AD, 4 with mild cognitive impairment) received a 90-min dynamic (S)-(18)F-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. Volume-of-interest (VOI)-based analysis was performed using plasma-input models; single-tissue and 2-tissue (2TCM) compartment models and plasma-input Logan and reference tissue models; and simplified reference tissue model (SRTM), reference Logan, and SUV ratio (SUVr). Cerebellum gray matter was used as the reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan, and SUVr. Regionally averaged voxel values were compared with VOI-based values from the optimal reference tissue model, and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40- and 60-min data were analyzed.
  
  
  RESULTS
  Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R(2)= 0.99, slope = 0.96). SRTM binding potential (BP(ND)) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R(2)= 1.00, slope ≈ 1.00) whereas SUVr(70-90)-1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R(2)= 0.99, slope = 1.03). SUVr(70-90)-1 values were almost 3 times higher than BP(ND) values in white matter and 1.5 times higher in gray matter. Simulations showed poorer accuracy and precision for SUVr(70-90)-1 values than for the other reference methods. SRTM BP(ND) and reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min.
  
  
  CONCLUSIONS
  SRTM BP(ND) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-(18)F-THK5117 DVR-1 parametric images with the greatest accuracy and precision and with a much lower white-matter signal than seen with SUVr(70-90)-1 images.
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: My
authors.initials: M
authors.lastname: Jonasson
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.affiliation: Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Chiotis
authors.affiliation: Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Laure
authors.initials: L
authors.lastname: Saint-Aubert
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Wilking
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Sprycha
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Borg
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Thibblin
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden Pre-clinical PET Platform, Uppsala University, Uppsala, Sweden; and.
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden PET Centre, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: PET Centre, Uppsala University Hospital, Uppsala, Sweden Pre-clinical PET Platform, Uppsala University, Uppsala, Sweden; and.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.affiliation: Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden agneta.k.nordberg@ki.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.affiliation: Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D003198:Computer Simulation; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging; D011804:Quinolines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D024801:Tauopathies / Q000000981:diagnostic imaging* / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C000604726:6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline; D000814:Aniline Compounds; D011804:Quinolines; D019275:Radiopharmaceuticals; D016875:tau Proteins
keywords: Alzheimer’s disease; kinetic modeling; parametric images; positron emission tomography; tau