title: Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus.
abstract: BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site.
  
  
  METHODS
  Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain.
  
  
  RESULTS
  Four of the 17 patients (23.5%) had amyloid-β pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-β levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%.
  
  
  CONCLUSIONS
  [(18)F]Flutemetamol detects brain amyloid-β in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.forename: Janek
authors.initials: J
authors.lastname: Frantzen
authors.forename: Ville
authors.initials: V
authors.lastname: Leinonen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Lonnrot
authors.forename: Aki
authors.initials: A
authors.lastname: Laakso
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
authors.forename: Anna
authors.initials: A
authors.lastname: Kotkansalo
authors.forename: Anne
authors.initials: A
authors.lastname: Koivisto
authors.forename: Juha
authors.initials: J
authors.lastname: Sajanti
authors.forename: Atte
authors.initials: A
authors.lastname: Karppinen
authors.forename: Hanna
authors.initials: H
authors.lastname: Lehto
authors.forename: Jaana
authors.initials: J
authors.lastname: Rummukainen
authors.forename: Chris
authors.initials: C
authors.lastname: Buckley
authors.forename: Adrian
authors.initials: A
authors.lastname: Smith
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jones
authors.forename: Paul
authors.initials: P
authors.lastname: Sherwin
authors.forename: Gill
authors.initials: G
authors.lastname: Farrar
authors.forename: Richard
authors.initials: R
authors.lastname: McLain
authors.forename: Marita
authors.initials: M
authors.lastname: Kailajarvi
authors.forename: Igor D
authors.initials: ID
authors.lastname: Grachev
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000814:Aniline Compounds; D052160:Benzothiazoles; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011446:Prospective Studies
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; C581552:flutemetamol