title: Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue.
abstract: BACKGROUND
  Florbetapir F 18 (F-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid (Aβ) plaques in human brain homogenates (Kd=3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and Aβ density measured by established neuropathologic methods.
  
  
  METHODS
  The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of Aβ identified by silver staining, thioflavin S staining, and immunohistochemistry.
  
  
  RESULTS
  There were strong quantitative correlations between florbetapir F 18 tissue binding and both Aβ plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of Aβ using 3 antibodies recognizing different epitopes of the Aβ peptide. Florbetapir F 18 did not bind to neurofibrillary tangles.
  
  
  CONCLUSIONS
  Florbetapir F 18 selectively binds Aβ in human brain tissue. The binding intensity was quantitatively correlated with the density of Aβ plaques identified by standard neuropathologic techniques and correlated with the density of Aβ measured by immunohistochemistry. As Aβ plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment.
authors.affiliation: Avid Radiopharmaceutical Inc., 3711 Market Street, 7th Floor, Philadelphia, PA 19104, USA.
authors.forename: Seok Rye
authors.initials: SR
authors.lastname: Choi
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Bedell
authors.forename: Simone P
authors.initials: SP
authors.lastname: Zehntner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krautkramer
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Skovronsky
authors.forename: Franz
authors.initials: F
authors.lastname: Hefti
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000814:Aniline Compounds / Q000032:analysis* / Q000737:chemistry; D001344:Autopsy; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005026:Ethylene Glycols / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging / Q000473:pathology; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000032:analysis*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir