18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial

Rik Vandenberghe; Koen Van Laere; Adrian Ivanoiu; Eric Salmon; Christine Bastin; Eric Triau; Steen Hasselbalch; Ian Law; Allan Andersen; Ejnar Alex Kørner; Lennart Minthon; Gaëtan Garraux; Natalie Nelissen; Guy Bormans; Chris Buckley; Rikard Owenius; Lennart Thurfjell; Gill Farrar; David J Brooks

doi:10.1002/ana.22068

18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial

Rik Vandenberghe, Koen Van Laere, Adrian Ivanoiu, Eric Salmon, Christine Bastin, Eric Triau, Steen Hasselbalch, Ian Law, Allan Andersen, Ejnar Alex Kørner, Lennart Minthon, Gaëtan Garraux, Natalie Nelissen, Guy Bormans, Chris Buckley, Rikard Owenius, Lennart Thurfjell, Gill Farrar, David J Brooks

Department of Clinical Medicine

480 Citations (Scopus)

Abstract

Objective: The most widely studied positron emission tomography ligand for in vivo β-amyloid imaging is ¹¹C-Pittsburgh compound B ( ¹¹C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the ¹⁸F-labeled PIB derivative ¹⁸F-flutemetamol could significantly enhance access to this novel technology. Methods: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of ¹⁸F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for ¹⁸F- flutemetamol and its parent molecule ¹¹C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of ¹⁸F-flutemetamol SUVRs in 5 of the AD subjects. Results: Blinded visual assessments of ¹⁸F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical ¹⁸F-flutemetamol SUVRs and ¹¹C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation: ¹⁸F-Flutemetamol performs similarly to the ¹¹C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.

Original language	English
Journal	Annals of Neurology
Volume	68
Issue number	3
Pages (from-to)	319-29
Number of pages	11
ISSN	0364-5134
DOIs	https://doi.org/10.1002/ana.22068
Publication status	Published - Sept 2010

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Vandenberghe, R., Van Laere, K., Ivanoiu, A., Salmon, E., Bastin, C., Triau, E., Hasselbalch, S., Law, I., Andersen, A., Kørner, E. A., Minthon, L., Garraux, G., Nelissen, N., Bormans, G., Buckley, C., Owenius, R., Thurfjell, L., Farrar, G., & Brooks, D. J. (2010). 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Annals of Neurology, 68(3), 319-29. https://doi.org/10.1002/ana.22068

Vandenberghe, R, Van Laere, K, Ivanoiu, A, Salmon, E, Bastin, C, Triau, E, Hasselbalch, S , Law, I, Andersen, A, Kørner, EA, Minthon, L, Garraux, G, Nelissen, N, Bormans, G, Buckley, C, Owenius, R, Thurfjell, L, Farrar, G & Brooks, DJ 2010, '18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial', Annals of Neurology, vol. 68, no. 3, pp. 319-29. https://doi.org/10.1002/ana.22068

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title = "18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial",

abstract = "Objective: The most widely studied positron emission tomography ligand for in vivo β-amyloid imaging is 11C-Pittsburgh compound B ( 11C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the 18F-labeled PIB derivative 18F-flutemetamol could significantly enhance access to this novel technology. Methods: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of 18F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for 18F- flutemetamol and its parent molecule 11C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of 18F-flutemetamol SUVRs in 5 of the AD subjects. Results: Blinded visual assessments of 18F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical 18F-flutemetamol SUVRs and 11C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation: 18F-Flutemetamol performs similarly to the 11C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.",

author = "Rik Vandenberghe and {Van Laere}, Koen and Adrian Ivanoiu and Eric Salmon and Christine Bastin and Eric Triau and Steen Hasselbalch and Ian Law and Allan Andersen and K{\o}rner, {Ejnar Alex} and Lennart Minthon and Ga{\"e}tan Garraux and Natalie Nelissen and Guy Bormans and Chris Buckley and Rikard Owenius and Lennart Thurfjell and Gill Farrar and Brooks, {David J}",

year = "2010",

month = sep,

doi = "10.1002/ana.22068",

language = "English",

volume = "68",

pages = "319--29",

journal = "Annals of Neurology",

issn = "0364-5134",

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T1 - 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial

AU - Vandenberghe, Rik

AU - Van Laere, Koen

AU - Ivanoiu, Adrian

AU - Salmon, Eric

AU - Bastin, Christine

AU - Triau, Eric

AU - Hasselbalch, Steen

AU - Law, Ian

AU - Andersen, Allan

AU - Kørner, Ejnar Alex

AU - Minthon, Lennart

AU - Garraux, Gaëtan

AU - Nelissen, Natalie

AU - Bormans, Guy

AU - Buckley, Chris

AU - Owenius, Rikard

AU - Thurfjell, Lennart

AU - Farrar, Gill

AU - Brooks, David J

PY - 2010/9

Y1 - 2010/9

N2 - Objective: The most widely studied positron emission tomography ligand for in vivo β-amyloid imaging is 11C-Pittsburgh compound B ( 11C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the 18F-labeled PIB derivative 18F-flutemetamol could significantly enhance access to this novel technology. Methods: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of 18F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for 18F- flutemetamol and its parent molecule 11C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of 18F-flutemetamol SUVRs in 5 of the AD subjects. Results: Blinded visual assessments of 18F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical 18F-flutemetamol SUVRs and 11C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation: 18F-Flutemetamol performs similarly to the 11C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.

AB - Objective: The most widely studied positron emission tomography ligand for in vivo β-amyloid imaging is 11C-Pittsburgh compound B ( 11C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the 18F-labeled PIB derivative 18F-flutemetamol could significantly enhance access to this novel technology. Methods: Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of 18F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for 18F- flutemetamol and its parent molecule 11C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of 18F-flutemetamol SUVRs in 5 of the AD subjects. Results: Blinded visual assessments of 18F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical 18F-flutemetamol SUVRs and 11C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation: 18F-Flutemetamol performs similarly to the 11C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.

U2 - 10.1002/ana.22068

DO - 10.1002/ana.22068

M3 - Journal article

SN - 0364-5134

VL - 68

SP - 319

EP - 329

JO - Annals of Neurology

JF - Annals of Neurology

IS - 3

ER -

18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial

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