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Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density

Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density
Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density

Importance: 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.

Design, setting and participants: 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.

Interventions: flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation.

Main outcomes and measures: 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 and relevence: 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.

Aged, Aged, 80 and over, Aniline Compounds, Benzothiazoles, Female, Fluorine Radioisotopes, Humans, Male, Middle Aged, Plaque, Amyloid, Positron-Emission Tomography, Single-Blind Method, Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
2168-6149
287-94
Curtis, Craig
8945dd4a-94f3-47e1-97dd-502a25067e6e
Gamez, Jose E
108246ad-6254-4b71-9db6-f1c65c9dc861
Singh, Upinder
97dc4624-1a55-434c-af2f-a2e0bb16e1f1
Sadowsky, Carl H
8ca0fbf5-ce3e-422d-be59-befb42bbd0e7
Villena, Teresa
1ba3dfd9-a253-4582-8695-5dc14e991865
Sabbagh, Marwan N
20e05fea-f200-4620-8c56-bb97d49dd1ea
Beach, Thomas G
03084824-6526-4b32-be61-5d278be9451c
Duara, Ranjan
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Fleisher, Adam S
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Frey, Kirk A
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Walker, Zuzana
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Hunjan, Arvinder
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Holmes, Clive
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Escovar, Yavir M
ce248f55-a446-4df1-b4b4-bce3e74df07c
Vera, Carla X
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Agronin, Marc E
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Ross, Joel
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Bozoki, Andrea
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Akinola, Mary
36768cdb-f1ea-437f-b7fa-5483dedafa11
Shi, Jiong
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Vandenberghe, Rik
c8e95a77-5c49-4c5d-9af2-53340342033f
Ikonomovic, Milos D
de01b5f4-087a-49f1-b7a4-3ba50935717e
Sherwin, Paul F
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Grachev, Igor D
70b5eb44-46de-41ce-a8a2-e64830b23391
Farrar, Gillian
d84b91fb-7304-417e-b3cb-8aaa8e8e26b3
Smith, Adrian P L
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Buckley, Christopher J
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McLain, Richard
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Salloway, Stephen
48e3aaa9-3328-4dfb-974b-81a4ba5ce32c
Curtis, Craig
8945dd4a-94f3-47e1-97dd-502a25067e6e
Gamez, Jose E
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Singh, Upinder
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Sadowsky, Carl H
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Villena, Teresa
1ba3dfd9-a253-4582-8695-5dc14e991865
Sabbagh, Marwan N
20e05fea-f200-4620-8c56-bb97d49dd1ea
Beach, Thomas G
03084824-6526-4b32-be61-5d278be9451c
Duara, Ranjan
083260da-5a8c-498a-9f86-9d4cf730a686
Fleisher, Adam S
51f3bb3c-cb68-4d2b-922b-5836d79b24ef
Frey, Kirk A
b38be2ef-39a3-4d0f-ae6c-6a072201b08c
Walker, Zuzana
4b450f01-7f2a-44a8-9161-f036637e1d5a
Hunjan, Arvinder
db5b6cf3-612b-4975-95a4-6891b6ba80d7
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Escovar, Yavir M
ce248f55-a446-4df1-b4b4-bce3e74df07c
Vera, Carla X
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Agronin, Marc E
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Ross, Joel
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Bozoki, Andrea
71180803-f3ce-41dd-89c4-4c2174858e78
Akinola, Mary
36768cdb-f1ea-437f-b7fa-5483dedafa11
Shi, Jiong
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Vandenberghe, Rik
c8e95a77-5c49-4c5d-9af2-53340342033f
Ikonomovic, Milos D
de01b5f4-087a-49f1-b7a4-3ba50935717e
Sherwin, Paul F
8537b475-f678-4e0c-be09-dadf7d6f75a4
Grachev, Igor D
70b5eb44-46de-41ce-a8a2-e64830b23391
Farrar, Gillian
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Smith, Adrian P L
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Buckley, Christopher J
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McLain, Richard
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Salloway, Stephen
48e3aaa9-3328-4dfb-974b-81a4ba5ce32c

Curtis, Craig, Gamez, Jose E, Singh, Upinder, Sadowsky, Carl H, Villena, Teresa, Sabbagh, Marwan N, Beach, Thomas G, Duara, Ranjan, Fleisher, Adam S, Frey, Kirk A, Walker, Zuzana, Hunjan, Arvinder, Holmes, Clive, Escovar, Yavir M, Vera, Carla X, Agronin, Marc E, Ross, Joel, Bozoki, Andrea, Akinola, Mary, Shi, Jiong, Vandenberghe, Rik, Ikonomovic, Milos D, Sherwin, Paul F, Grachev, Igor D, Farrar, Gillian, Smith, Adrian P L, Buckley, Christopher J, McLain, Richard and Salloway, Stephen (2015) Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA Neurology, 72 (3), 287-94. (doi:10.1001/jamaneurol.2014.4144).

Record type: Article

Abstract

Importance: 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.

Design, setting and participants: 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.

Interventions: flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation.

Main outcomes and measures: 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 and relevence: 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.

Full text not available from this repository.

More information

Published date: March 2015
Keywords: Aged, Aged, 80 and over, Aniline Compounds, Benzothiazoles, Female, Fluorine Radioisotopes, Humans, Male, Middle Aged, Plaque, Amyloid, Positron-Emission Tomography, Single-Blind Method, Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416110
URI: https://eprints.soton.ac.uk/id/eprint/416110
ISSN: 2168-6149
PURE UUID: fcdfc505-f8cc-48b3-aa51-cf7313470093
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 04 Dec 2017 17:30
Last modified: 17 Jul 2019 17:42

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Contributors

Author: Craig Curtis
Author: Jose E Gamez
Author: Upinder Singh
Author: Carl H Sadowsky
Author: Teresa Villena
Author: Marwan N Sabbagh
Author: Thomas G Beach
Author: Ranjan Duara
Author: Adam S Fleisher
Author: Kirk A Frey
Author: Zuzana Walker
Author: Arvinder Hunjan
Author: Clive Holmes ORCID iD
Author: Yavir M Escovar
Author: Carla X Vera
Author: Marc E Agronin
Author: Joel Ross
Author: Andrea Bozoki
Author: Mary Akinola
Author: Jiong Shi
Author: Rik Vandenberghe
Author: Milos D Ikonomovic
Author: Paul F Sherwin
Author: Igor D Grachev
Author: Gillian Farrar
Author: Adrian P L Smith
Author: Christopher J Buckley
Author: Richard McLain
Author: Stephen Salloway

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