title: Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density.
abstract: OBJECTIVE
  In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease.
  
  
  OBJECTIVE
  To determine the sensitivity and specificity of positron emission tomography imaging with flutemetamol injection labeled with radioactive fluorine 18 to detect β-amyloid in the brain using neuropathologically determined neuritic plaque levels as the standard of truth.
  
  
  METHODS
  Open-label multicenter imaging study that took place at dementia clinics, memory centers, and hospice centers in the United States and England from June 22, 2010, to November 23, 2011. Participants included terminally ill patients who were 55 years or older with a life expectancy of less than 1 year.
  
  
  METHODS
  Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation.
  
  
  METHODS
  Sensitivity and specificity of flutemetamol injection labeled with radioactive fluorine 18 positron emission tomography imaging for brain β-amyloid. Images were reviewed without and with computed tomography scans and classified as positive or negative for β-amyloid by 5 readers who were blind to patient information. In patients who died, neuropathologically determined neuritic plaque levels were used to confirm scan interpretations and determine sensitivity and specificity.
  
  
  RESULTS
  Of 176 patients with evaluable images, 68 patients (38%) died during the study, were autopsied, and had neuritic plaque levels determined; 25 brains (37%) were β-amyloid negative; and 43 brains (63%) were β-amyloid positive. Imaging was performed a mean of 3.5 months (range, 0 to 13 months) before death. Sensitivity without computed tomography was 81% to 93% (median, 88%). Median specificity was 88%, with 4 of 5 of the readers having specificity greater than 80%. When scans were interpreted with computed tomography images, sensitivity and specificity improved for most readers but the differences were not significant. The area under the receiver operating curve was 0.90. There were no clinically meaningful findings in safety parameters.
  
  
  CONCLUSIONS
  This study showed that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity in an end-of-life population. In vivo detection of brain β-amyloid plaque density may increase diagnostic accuracy in cognitively impaired patients.
authors.affiliation: Compass Research, Orlando, Florida.
authors.forename: Craig
authors.initials: C
authors.lastname: Curtis
authors.affiliation: Galiz Research, Miami Springs, Florida.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Gamez
authors.affiliation: Geriatric Solutions, Las Vegas, Nevada.
authors.forename: Upinder
authors.initials: U
authors.lastname: Singh
authors.affiliation: Department of Neurology, Nova SE University, Ft Lauderdale, Florida.
authors.forename: Carl H
authors.initials: CH
authors.lastname: Sadowsky
authors.affiliation: Premiere Research Institute, West Palm Beach, Florida.
authors.forename: Teresa
authors.initials: T
authors.lastname: Villena
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Mount Sinai Medical Center, Wien Center for AD, Miami Beach, Florida.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Duara
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona8is now with Eli Lilly and Company, Indianapolis, Indiana9is now with the Department of Neurosciences, University of California, San Diego, San Diego.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.affiliation: Department of Radiology, Nuclear Medicine, University of Michigan, Ann Arbor.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.affiliation: Division of Psychiatry, University College London, England12North Essex Partnership University NHS Foundation Trust, London, England.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Walker
authors.affiliation: North Essex Partnership University NHS Foundation Trust, Essex, England.
authors.forename: Arvinder
authors.initials: A
authors.lastname: Hunjan
authors.affiliation: Clinical Experimental Science, University of Southampton, Southampton, Hampshire, England.
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.affiliation: VERITAS Research, Miami Lakes, Florida.
authors.forename: Yavir M
authors.initials: YM
authors.lastname: Escovar
authors.affiliation: VERITAS Research, Miami Lakes, Florida.
authors.forename: Carla X
authors.initials: CX
authors.lastname: Vera
authors.affiliation: Mental Health and Clinical Research, Miami Jewish Health Systems, Miami, Florida17Department of Psychiatry and Neurology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Agronin
authors.affiliation: Memory Enhancement Center, Eatontown, New Jersey.
authors.forename: Joel
authors.initials: J
authors.lastname: Ross
authors.affiliation: Cognitive and Geriatric Neurology Team, Neurology and Radiology, Michigan State University, East Lansing.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bozoki
authors.affiliation: Kennington Health Centre, Oxford, England.
authors.forename: Mary
authors.initials: M
authors.lastname: Akinola
authors.affiliation: Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona.
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.affiliation: Medical Affairs, GE Healthcare-Life Sciences, Princeton, New Jersey.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Sherwin
authors.affiliation: Medical Affairs, GE Healthcare-Life Sciences, Princeton, New Jersey25is now with Novartis Consumer Health, Parsippany, New Jersey26is now with Genpact Pharmalink, Short Hills, New Jersey.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Grachev
authors.affiliation: Life Sciences, GE Healthcare, Amersham, Buckinghamshire, England.
authors.forename: Gillian
authors.initials: G
authors.lastname: Farrar
authors.affiliation: Life Sciences, GE Healthcare, Amersham, Buckinghamshire, England.
authors.forename: Adrian P L
authors.initials: AP
authors.lastname: Smith
authors.affiliation: Life Sciences, GE Healthcare, Amersham, Buckinghamshire, England.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Buckley
authors.affiliation: PFP Statistical Consulting LLC, Livonia, Michigan.
authors.forename: Richard
authors.initials: R
authors.lastname: McLain
authors.affiliation: Department of Neurology and the Memory and Aging Program, Butler Hospital, Providence, Rhode Island30Department of Neurology and Psychiatry, Warren Alpert Medical School, Providence, Rhode Island31Brown University, Providence, Rhode Island.
authors.forename: Stephen
authors.initials: S
authors.lastname: Salloway
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds; D052160:Benzothiazoles; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000523:psychology; D049268:Positron-Emission Tomography / Q000592:standards*; D016037:Single-Blind Method
chemical_list: D000814:Aniline Compounds; D052160:Benzothiazoles; D005462:Fluorine Radioisotopes; C581552:flutemetamol