title: Comparison of Early-Phase 11C-Deuterium-l-Deprenyl and 11C-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease.
abstract: The PET tracer (11)C-deuterium-L-deprenyl ((11)C-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase (11)C-DED and (11)C-Pittsburgh compound B ((11)C-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which (11)C-DED binding is influenced by brain perfusion was investigated.
  
  
  
  (11)C-DED, (11)C-PiB, and (18)F-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify (11)C-DED binding. A simplified reference tissue model was applied to both (11)C-DED and (11)C-PiB to measure brain perfusion relative to the cerebellar gray matter (R1) and binding potentials. (11)C-PiB retention and (18)F-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs).
  
  
  
  The strongest within-subject correlations with the corresponding R1 values (R1,DED and R1,PiB, respectively) and with (18)F-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R1,DED/R1,PiB and with (18)F-FDG uptake, whereas (11)C-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal (18)F-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls.
  
  
  
  The 1- to 4-min early-frame intervals of (11)C-DED or (11)C-PiB are suitable surrogate measures for brain perfusion. (11)C-DED binding is independent of brain perfusion, and thus (11)C-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase (11)C-DED and (11)C-PiB perfusion appear to provide complementary rather than redundant information.
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Rodriguez-Vieitez
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Wolfson Molecular Imaging Centre, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Carter
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Chiotis
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Laure
authors.initials: L
authors.lastname: Saint-Aubert
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Schöll
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Department of Psychology, Stockholm University, Stockholm, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.affiliation: Department of Surgical Sciences, Section of Nuclear Medicine & PET, Uppsala University, Uppsala, Sweden; and.
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.affiliation: Deparment of Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.affiliation: Division of Translational Alzheimer Neurobiology, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, 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
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D000814:Aniline Compounds; D002531:Cerebellum / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology; D003903:Deuterium; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18; D005911:Gliosis; D066128:Gray Matter / Q000098:blood supply / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011149:Pons / Q000098:blood supply / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D012642:Selegiline; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D012642:Selegiline; D003903:Deuterium
keywords: amyloid; astrocytosis; brain perfusion; early-phase PET