Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study

Osama Sabri; Marwan N. Sabbagh; John Seibyl; Henryk Barthel; Hiroyasu Akatsu; Yasuomi Ouchi; Kohei Senda; Shigeo Murayama; Kenji Ishii; Masaki Takao; Thomas G. Beach; Christopher C. Rowe; James B. Leverenz; Bernardino Ghetti; James W. Ironside; Ana M. Catafau; Andrew W. Stephens; Andre Mueller; Norman Koglin; Anja Hoffmann; Katrin Roth; Cornelia Reininger; Walter J. Schulz-Schaeffer

doi:10.1016/j.jalz.2015.02.004

Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study

Osama Sabri^*, Marwan N. Sabbagh, John Seibyl, Henryk Barthel, Hiroyasu Akatsu, Yasuomi Ouchi, Kohei Senda, Shigeo Murayama, Kenji Ishii, Masaki Takao, Thomas G. Beach, Christopher C. Rowe, James B. Leverenz, Bernardino Ghetti, James W. Ironside, Ana M. Catafau, Andrew W. Stephens, Andre Mueller, Norman Koglin, Anja HoffmannKatrin Roth, Cornelia Reininger, Walter J. Schulz-Schaeffer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Abstract Background Evaluation of brain β-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. Methods Open-label, nonrandomized, multicenter, phase 3 study to validate the ¹⁸F-labeled β-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. Results Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic β-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic β-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate β-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. Conclusions Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic β-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. Trial registration ClinicalTrials.gov NCT01020838.

Original language	English
Article number	1958
Pages (from-to)	964-974
Number of pages	11
Journal	Alzheimer's & Dementia
Volume	11
Issue number	8
DOIs	https://doi.org/10.1016/j.jalz.2015.02.004
Publication status	Published - 1 Aug 2015

Keywords

Amyloid
Florbetaben
Histopathology
PET

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10.1016/j.jalz.2015.02.004

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Sabri, O., Sabbagh, M. N., Seibyl, J., Barthel, H., Akatsu, H., Ouchi, Y., Senda, K., Murayama, S., Ishii, K., Takao, M., Beach, T. G., Rowe, C. C., Leverenz, J. B., Ghetti, B., Ironside, J. W., Catafau, A. M., Stephens, A. W., Mueller, A., Koglin, N., ... Schulz-Schaeffer, W. J. (2015). Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study. Alzheimer's & Dementia, 11(8), 964-974. [1958]. https://doi.org/10.1016/j.jalz.2015.02.004

Sabri, Osama ; Sabbagh, Marwan N. ; Seibyl, John ; Barthel, Henryk ; Akatsu, Hiroyasu ; Ouchi, Yasuomi ; Senda, Kohei ; Murayama, Shigeo ; Ishii, Kenji ; Takao, Masaki ; Beach, Thomas G. ; Rowe, Christopher C. ; Leverenz, James B. ; Ghetti, Bernardino ; Ironside, James W. ; Catafau, Ana M. ; Stephens, Andrew W. ; Mueller, Andre ; Koglin, Norman ; Hoffmann, Anja ; Roth, Katrin ; Reininger, Cornelia ; Schulz-Schaeffer, Walter J. / Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease : Phase 3 study. In: Alzheimer's & Dementia. 2015 ; Vol. 11, No. 8. pp. 964-974.

@article{63b48d04324347739915de7e827fad99,

title = "Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study",

abstract = "Abstract Background Evaluation of brain β-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. Methods Open-label, nonrandomized, multicenter, phase 3 study to validate the 18F-labeled β-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. Results Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic β-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic β-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate β-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. Conclusions Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic β-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. Trial registration ClinicalTrials.gov NCT01020838.",

keywords = "Amyloid, Florbetaben, Histopathology, PET",

author = "Osama Sabri and Sabbagh, {Marwan N.} and John Seibyl and Henryk Barthel and Hiroyasu Akatsu and Yasuomi Ouchi and Kohei Senda and Shigeo Murayama and Kenji Ishii and Masaki Takao and Beach, {Thomas G.} and Rowe, {Christopher C.} and Leverenz, {James B.} and Bernardino Ghetti and Ironside, {James W.} and Catafau, {Ana M.} and Stephens, {Andrew W.} and Andre Mueller and Norman Koglin and Anja Hoffmann and Katrin Roth and Cornelia Reininger and Schulz-Schaeffer, {Walter J.}",

year = "2015",

month = aug,

day = "1",

doi = "10.1016/j.jalz.2015.02.004",

language = "English",

volume = "11",

pages = "964--974",

journal = "Alzheimer's & Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "8",

}

Sabri, O, Sabbagh, MN, Seibyl, J, Barthel, H, Akatsu, H, Ouchi, Y, Senda, K, Murayama, S, Ishii, K, Takao, M, Beach, TG, Rowe, CC, Leverenz, JB, Ghetti, B, Ironside, JW, Catafau, AM, Stephens, AW, Mueller, A, Koglin, N, Hoffmann, A, Roth, K, Reininger, C & Schulz-Schaeffer, WJ 2015, 'Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study', Alzheimer's & Dementia, vol. 11, no. 8, 1958, pp. 964-974. https://doi.org/10.1016/j.jalz.2015.02.004

Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease : Phase 3 study. / Sabri, Osama; Sabbagh, Marwan N.; Seibyl, John; Barthel, Henryk; Akatsu, Hiroyasu; Ouchi, Yasuomi; Senda, Kohei; Murayama, Shigeo; Ishii, Kenji; Takao, Masaki; Beach, Thomas G.; Rowe, Christopher C.; Leverenz, James B.; Ghetti, Bernardino; Ironside, James W.; Catafau, Ana M.; Stephens, Andrew W.; Mueller, Andre; Koglin, Norman; Hoffmann, Anja; Roth, Katrin; Reininger, Cornelia; Schulz-Schaeffer, Walter J.

In: Alzheimer's & Dementia, Vol. 11, No. 8, 1958, 01.08.2015, p. 964-974.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease

T2 - Phase 3 study

AU - Sabri, Osama

AU - Sabbagh, Marwan N.

AU - Seibyl, John

AU - Barthel, Henryk

AU - Akatsu, Hiroyasu

AU - Ouchi, Yasuomi

AU - Senda, Kohei

AU - Murayama, Shigeo

AU - Ishii, Kenji

AU - Takao, Masaki

AU - Beach, Thomas G.

AU - Rowe, Christopher C.

AU - Leverenz, James B.

AU - Ghetti, Bernardino

AU - Ironside, James W.

AU - Catafau, Ana M.

AU - Stephens, Andrew W.

AU - Mueller, Andre

AU - Koglin, Norman

AU - Hoffmann, Anja

AU - Roth, Katrin

AU - Reininger, Cornelia

AU - Schulz-Schaeffer, Walter J.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Abstract Background Evaluation of brain β-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. Methods Open-label, nonrandomized, multicenter, phase 3 study to validate the 18F-labeled β-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. Results Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic β-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic β-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate β-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. Conclusions Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic β-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. Trial registration ClinicalTrials.gov NCT01020838.

AB - Abstract Background Evaluation of brain β-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. Methods Open-label, nonrandomized, multicenter, phase 3 study to validate the 18F-labeled β-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. Results Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic β-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic β-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate β-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. Conclusions Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic β-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. Trial registration ClinicalTrials.gov NCT01020838.

KW - Amyloid

KW - Florbetaben

KW - Histopathology

KW - PET

UR - http://www.scopus.com/inward/record.url?scp=84939264152&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2015.02.004

DO - 10.1016/j.jalz.2015.02.004

M3 - Article

AN - SCOPUS:84939264152

VL - 11

SP - 964

EP - 974

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 8

M1 - 1958

ER -

Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study

Abstract

Keywords

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