title: In Vivo Comparison of Tau Radioligands18F-THK-5351 and18F-THK-5317.
abstract: This study compared the in vivo imaging characteristics of tau PET ligands18F-THK-5351 and18F-THK-5317 in the context of Alzheimer disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and SUV ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification.Methods:Twenty-eight subjects (mean age ± SD, 71 ± 7 y) underwent either dynamic 90-min18F-THK-5317 or18F-THK-5351 PET scans. Bland-Altman plots were used to compare the simplified reference tissue method, multilinear reference tissue method (MRTM2), and Logan reference tissue DVR estimates and to assess temporal stability of SUVR windows using cerebellar gray matter as a reference region. In vivo kinetics and DVR estimates were directly compared for 10 subjects who underwent both18F-THK-5317 and18F-THK-5351 PET scans.Results:THK-5351 exhibited faster cerebellar gray matter clearance, faster cortical white matter clearance, and higher DVR estimates in AD tau-associated regions of interest than THK-5317. The MRTM2 method produced the most reliable DVR estimates for both tracers, particularly when scan duration was shortened to 60 min. SUVR stability was observed 50-70 min after injection for both tracers. Parametric images revealed differences between MRTM2, Logan, and SUVR binding in white matter regions for THK-5317.Conclusion:THK-5317 and THK-5351 show promise for in vivo detection of AD tau. THK-5351 has more favorable pharmacokinetics and imaging characteristics than THK-5317.
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin tbetthauser@wisc.edu.|Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: Betthauser
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.|Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lao
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Division of Radiopharmaceutical Neuroimaging, Tohoku University, Sendai, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Stone
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Veterans Hospital, Madison, Wisconsin; and.|Wisconsin Alzheimer's Institute, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.|Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D000631:Aminopyridines / Q000493:pharmacokinetics*; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011804:Quinolines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C000604726:6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline; D000631:Aminopyridines; D000814:Aniline Compounds; D015415:Biomarkers; D011804:Quinolines; D019275:Radiopharmaceuticals; C000608225:THK5351; D016875:tau Proteins
keywords: Alzheimer’s disease; THK; positron emission tomography; quantitation; tau