title: In vitro characterization of [18F]-florbetaben, an Aβ imaging radiotracer.
abstract: OBJECTIVE
  Amyloid-β (Aβ) plaques are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of Aβ plaques may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [(11)C]-PiB is the most widely used Aβ positron emission tomography (PET) radiotracer, due to the short half-life of (11)C (20 min), its application is limited to centers with an on-site cyclotron and (11)C radiochemistry expertise. Therefore, novel [(18)F] (half-life 110 min)-labeled Aβ PET tracers have been developed. We have demonstrated that [(18)F]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [(18)F]-florbetaben-PET retention matched the reported postmortem distribution of Aβ plaques, the nature of [(18)F]-florbetaben binding to other pathological lesions comprising misfolded proteins needs further assessment. The objective of this study was to determine whether Florbetaben selectively binds to Aβ plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and α-synuclein aggregates).
  
  
  METHODS
  Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [(18)F]-florbetaben autoradiography and [(3)H]-florbetaben high-resolution emulsion autoradiography and [(19)F]-florbetaben fluorescence microscopy.
  
  
  RESULTS
  Both autoradiographical analyses demonstrated that Florbetaben exclusively bound Aβ plaques in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [(19)F]-florbetaben did not bind to α-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [(19)F]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified Aβ plaques in all brain regions examined.
  
  
  CONCLUSIONS
  This study provides further evidence that [(18)F]-florbetaben-PET is a highly selective radiotracer to assess Aβ plaque deposition in the brain.
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Fodero-Tavoletti
authors.forename: Damian
authors.initials: D
authors.lastname: Brockschnieder
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Lucas
authors.initials: L
authors.lastname: Martin
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Connor
authors.forename: Andrea
authors.initials: A
authors.lastname: Thiele
authors.forename: Mathias
authors.initials: M
authors.lastname: Berndt
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Ludger
authors.initials: L
authors.lastname: Dinkelborg
authors.forename: Thomas
authors.initials: T
authors.lastname: Dyrks
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging; D058225:Plaque, Amyloid / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011849:Radioactive Tracers; D013267:Stilbenes / Q000378:metabolism*; D013379:Substrate Specificity; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D011849:Radioactive Tracers; D013267:Stilbenes; D051844:alpha-Synuclein; D016875:tau Proteins; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene