title: Modeling Strategies for Quantification of In Vivo18F-AV-1451 Binding in Patients with Tau Pathology.
abstract: Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer disease (AD). In vivo imaging with PET may offer important insights into pathophysiologic mechanisms, diagnosis, and disease progression. We describe different strategies for quantification of18F-AV-1451 (T807) tau binding, including models with blood sampling and noninvasive alternatives.Methods:Fifteen subjects (4 controls, 6 AD, 3 progressive supranuclear palsy, 2 cortico basal syndrome) underwent 180-min PET with18F-AV-1451 and arterial blood sampling. Modeling with arterial input functions included 1-, 2-, and 3-tissue-compartment models and the Logan plot. Using the cerebellum as reference region, we applied the simplified reference tissue model 2 and Logan reference plot. Finally, simplified outcome measures were calculated as ratio, with reference to cerebellar concentrations (SUV ratio [SUVR]) and SUVs.Results:Tissue compartment models were not able to describe the kinetics of18F-AV-1451, with poor fits in 33%-53% of cortical regions and 80% in subcortical areas. In contrast, the Logan plot showed excellent fits and parameter variance (total volume of distribution SE < 5%). Compared with the 180-min arterial-based Logan model, strong agreement was obtained for the Logan reference plot also for a reduced scan time of 100 min (R2= 0.91) and SUVR 100-120 min (R2= 0.94), with 80-100 min already representing a reasonable compromise between duration and accuracy (R2= 0.93). Time-activity curves and kinetic parameters were equal for cortical regions and the cerebellum in control subjects but different in the putamen. Cerebellar total volumes of distribution were higher in controls than patients. For these methods, increased cortical binding was observed for AD patients and to some extent for cortico basal syndrome, but not progressive supranuclear palsy.Conclusion:The Logan plot provided the best estimate of tau binding using arterial input functions. Assuming that the cerebellum is a valid reference region, simplified methods seem to provide robust alternatives for quantification, such as the Logan reference plot with 100-min scan time. Furthermore, SUVRs between target and cerebellar activities obtained from an 80- to 100-min static scan offer promising potential for clinical routine application.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria andreas.hahn@meduniwien.ac.at oskar.hansson@med.lu.se.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schain
authors.affiliation: Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Erlandsson
authors.affiliation: Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Sjölin
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: James
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
authors.forename: Olof T
authors.initials: OT
authors.lastname: Strandberg
authors.affiliation: Department of Clinical Neurophysiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hägerström
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Skåne University Hospital, Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Jögi
authors.affiliation: Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Tomas G
authors.initials: TG
authors.lastname: Olsson
authors.affiliation: Department of Neurology, Skåne University Hospital, Lund, Sweden; and.
authors.forename: Ruben
authors.initials: R
authors.lastname: Smith
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden andreas.hahn@meduniwien.ac.at oskar.hansson@med.lu.se.|Memory Clinic, Skåne University Hospital, Malmö, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; 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: kinetic modeling; positron emission tomography; quantification; tau imaging