title: Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer's disease.
abstract: OBJECTIVE
  [(18)F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD).
  
  
  METHODS
  This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1 - 9 min after administration of both tracers and 40 - 70 min and 90 - 110 min after administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated.
  
  
  RESULTS
  Regional visual scores of early Aβ tracer and [(18)F]FDG PET images were significantly correlated (Spearman's ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [(18)F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [(18)F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison.
  
  
  CONCLUSIONS
  Early [(18)F]FBB and [(11)C]PiB PET brain images are similar to [(18)F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [(18)F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany. solveig.tiepolt@medizin.uni-leipzig.de.
authors.forename: Solveig
authors.initials: S
authors.lastname: Tiepolt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.|Integrated Research and Treatment Center (IFB) Adiposity Diseases, Leipzig, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Luthardt
authors.affiliation: Clinic for Cognitive Neurology & Max Planck Institute for Human Cognitive & Brain Sciences, University of Leipzig, Leipzig, Germany.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Schroeter
authors.affiliation: Department of Neuroradiology, University of Leipzig, Leipzig, Germany.
authors.forename: Karl-Titus
authors.initials: KT
authors.lastname: Hoffmann
authors.affiliation: Department of Neurology, University of Leipzig, Leipzig, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Weise
authors.affiliation: Department of Psychiatry, University of Leipzig, Leipzig, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gertz
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.|Integrated Research and Treatment Center (IFB) Adiposity Diseases, Leipzig, Germany.
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.
authors.forename: Henryk
authors.initials: H
authors.lastname: Barthel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D000814:Aniline Compounds / Q000378:metabolism; D001692:Biological Transport; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D013267:Stilbenes / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013267:Stilbenes; D013844:Thiazoles; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
keywords: Alzheimer’s disease; Aβ tracers; Dual time-point; [11C]PiB PET; [18F]FBB PET