18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial

Nikhil V Joshi; Alex T Vesey; Michelle C Williams; Anoop SV Shah; Patrick A Calvert; Felicity H M Craighead; Su Ern Yeoh; William Wallace; Donald Salter; Alison M Fletcher; Edwin J R van Beek; Andrew D Flapan; Neal G Uren; Miles W H Behan; Nicholas L M Cruden; Nicholas L Mills; Keith A A Fox; James H F Rudd; Marc R Dweck; David E Newby

doi:10.1016/S0140-6736(13)61754-7

¹⁸F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial

Nikhil V Joshi^*, Alex T Vesey, Michelle C Williams, Anoop SV Shah, Patrick A Calvert, Felicity H M Craighead, Su Ern Yeoh, William Wallace, Donald Salter, Alison M Fletcher, Edwin J R van Beek, Andrew D Flapan, Neal G Uren, Miles W H Behan, Nicholas L M Cruden, Nicholas L Mills, Keith A A Fox, James H F Rudd, Marc R Dweck, David E Newby

^*Corresponding author for this work

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

Abstract

Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers ¹⁸F-sodium fluoride (¹⁸F-NaF) and ¹⁸F-fluorodeoxyglucose (18F-FDG).

Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent ¹⁸F-NaF and ¹⁸F-FDG PET-CT, and invasive coronary angiography. ¹⁸F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of ¹⁸F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.

Findings: In 37 (93%) patients with myocardial infarction, the highest coronary ¹⁸F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40–2·25] vs highest non-culprit 1·24 [1·06–1·38], p<0·0001). By contrast, coronary ¹⁸F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40–2·13] vs 1·58 [1·28–2·01], p=0·34). Marked ¹⁸F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal ¹⁸F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61–2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09–1·19] vs 1·01 [0·94–1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21–29] vs 18% [14–22], p=0·001).

Interpretation: ¹⁸F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.

Funding: Chief Scientist Office Scotland and British Heart Foundation.

Original language	English
Pages (from-to)	705-713
Number of pages	9
Journal	The Lancet
Volume	383
Issue number	9918
Early online date	11 Nov 2013
DOIs	https://doi.org/10.1016/S0140-6736(13)61754-7
Publication status	Published - 22 Feb 2014

Keywords

ACUTE MYOCARDIAL-INFARCTION
VULNERABLE PLAQUE
VASCULAR CALCIFICATION
ARTERY-DISEASE
INTRAVASCULAR ULTRASOUND
AORTIC-STENOSIS
F-18-FDG UPTAKE
FLUORIDE UPTAKE
IN-VIVO
INFLAMMATION

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18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques a prospective clinical trial
Copyright © 2013 Joshi et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.
Final published version, 2.86 MBLicence: Creative Commons: Attribution (CC-BY)

Role of 18F-Fluoride imaging as a novel marker of plaque instability
Newby, D.
UK-based charities
1/08/12 → 31/07/14
Project: Research
NOVEL IMAGING APPROACHES TO IDENTIFY UNSTABLE ATHEROSCLEROTIC CORONARY PLAQUES
Newby, D.
UK central government bodies/local authorities, health and hospital authorities
1/11/11 → 30/04/13
Project: Research
BHF Scholarship scheme - Dr Dweck
Newby, D.
UK-based charities
1/12/09 → 28/02/11
Project: Research

Marc Dweck
- mdweckstaffmail.ed.acuk
- Deanery of Clinical Sciences - Personal Chair of Clinical Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active (Research Assistant)
David Newby
- d.e.newbyed.acuk
- Deanery of Clinical Sciences - BHF Duke of Edinburgh Chair of Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active
Edwin van Beek
- edwin-vanbeeked.acuk
- Deanery of Clinical Sciences - SINAPSE Chair of Clinical Radiology
- Edinburgh Neuroscience
- Edinburgh Imaging
- Centre for Cardiovascular Science
Person: Academic: Research Active

Cite this

Joshi, N. V., Vesey, A. T., Williams, M. C., Shah, A. SV., Calvert, P. A., Craighead, F. H. M., Yeoh, S. E., Wallace, W., Salter, D., Fletcher, A. M., van Beek, E. J. R., Flapan, A. D., Uren, N. G., Behan, M. W. H., Cruden, N. L. M., Mills, N. L., Fox, K. A. A., Rudd, J. H. F., Dweck, M. R., & Newby, D. E. (2014). ¹⁸F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. The Lancet, 383(9918), 705-713. https://doi.org/10.1016/S0140-6736(13)61754-7

@article{3b967677125041a0bffe46ab28f68e6e,

title = "18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial",

abstract = "Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG).Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-NaF and 18F-FDG PET-CT, and invasive coronary angiography. 18F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of 18F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.Findings: In 37 (93%) patients with myocardial infarction, the highest coronary 18F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40–2·25] vs highest non-culprit 1·24 [1·06–1·38], p<0·0001). By contrast, coronary 18F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40–2·13] vs 1·58 [1·28–2·01], p=0·34). Marked 18F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal 18F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61–2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09–1·19] vs 1·01 [0·94–1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21–29] vs 18% [14–22], p=0·001).Interpretation: 18F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.Funding: Chief Scientist Office Scotland and British Heart Foundation.",

keywords = "ACUTE MYOCARDIAL-INFARCTION, VULNERABLE PLAQUE, VASCULAR CALCIFICATION, ARTERY-DISEASE, INTRAVASCULAR ULTRASOUND, AORTIC-STENOSIS, F-18-FDG UPTAKE, FLUORIDE UPTAKE, IN-VIVO, INFLAMMATION",

author = "Joshi, {Nikhil V} and Vesey, {Alex T} and Williams, {Michelle C} and Shah, {Anoop SV} and Calvert, {Patrick A} and Craighead, {Felicity H M} and Yeoh, {Su Ern} and William Wallace and Donald Salter and Fletcher, {Alison M} and {van Beek}, {Edwin J R} and Flapan, {Andrew D} and Uren, {Neal G} and Behan, {Miles W H} and Cruden, {Nicholas L M} and Mills, {Nicholas L} and Fox, {Keith A A} and Rudd, {James H F} and Dweck, {Marc R} and Newby, {David E}",

year = "2014",

month = feb,

day = "22",

doi = "10.1016/S0140-6736(13)61754-7",

language = "English",

volume = "383",

pages = "705--713",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier",

number = "9918",

}

Joshi, NV, Vesey, AT, Williams, MC, Shah, ASV, Calvert, PA, Craighead, FHM, Yeoh, SE, Wallace, W, Salter, D, Fletcher, AM, van Beek, EJR, Flapan, AD, Uren, NG, Behan, MWH, Cruden, NLM, Mills, NL , Fox, KAA, Rudd, JHF, Dweck, MR & Newby, DE 2014, '¹⁸F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial', The Lancet, vol. 383, no. 9918, pp. 705-713. https://doi.org/10.1016/S0140-6736(13)61754-7

TY - JOUR

T1 - 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial

AU - Joshi, Nikhil V

AU - Vesey, Alex T

AU - Williams, Michelle C

AU - Shah, Anoop SV

AU - Calvert, Patrick A

AU - Craighead, Felicity H M

AU - Yeoh, Su Ern

AU - Wallace, William

AU - Salter, Donald

AU - Fletcher, Alison M

AU - van Beek, Edwin J R

AU - Flapan, Andrew D

AU - Uren, Neal G

AU - Behan, Miles W H

AU - Cruden, Nicholas L M

AU - Mills, Nicholas L

AU - Fox, Keith A A

AU - Rudd, James H F

AU - Dweck, Marc R

AU - Newby, David E

PY - 2014/2/22

Y1 - 2014/2/22

N2 - Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG).Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-NaF and 18F-FDG PET-CT, and invasive coronary angiography. 18F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of 18F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.Findings: In 37 (93%) patients with myocardial infarction, the highest coronary 18F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40–2·25] vs highest non-culprit 1·24 [1·06–1·38], p<0·0001). By contrast, coronary 18F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40–2·13] vs 1·58 [1·28–2·01], p=0·34). Marked 18F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal 18F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61–2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09–1·19] vs 1·01 [0·94–1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21–29] vs 18% [14–22], p=0·001).Interpretation: 18F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.Funding: Chief Scientist Office Scotland and British Heart Foundation.

AB - Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG).Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-NaF and 18F-FDG PET-CT, and invasive coronary angiography. 18F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of 18F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.Findings: In 37 (93%) patients with myocardial infarction, the highest coronary 18F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40–2·25] vs highest non-culprit 1·24 [1·06–1·38], p<0·0001). By contrast, coronary 18F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40–2·13] vs 1·58 [1·28–2·01], p=0·34). Marked 18F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal 18F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61–2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09–1·19] vs 1·01 [0·94–1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21–29] vs 18% [14–22], p=0·001).Interpretation: 18F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.Funding: Chief Scientist Office Scotland and British Heart Foundation.

KW - ACUTE MYOCARDIAL-INFARCTION

KW - VULNERABLE PLAQUE

KW - VASCULAR CALCIFICATION

KW - ARTERY-DISEASE

KW - INTRAVASCULAR ULTRASOUND

KW - AORTIC-STENOSIS

KW - F-18-FDG UPTAKE

KW - FLUORIDE UPTAKE

KW - IN-VIVO

KW - INFLAMMATION

U2 - 10.1016/S0140-6736(13)61754-7

DO - 10.1016/S0140-6736(13)61754-7

M3 - Article

C2 - 24224999

VL - 383

SP - 705

EP - 713

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9918

ER -

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial

Abstract

Keywords

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Projects

Role of 18F-Fluoride imaging as a novel marker of plaque instability

NOVEL IMAGING APPROACHES TO IDENTIFY UNSTABLE ATHEROSCLEROTIC CORONARY PLAQUES

BHF Scholarship scheme - Dr Dweck

Profiles

Marc Dweck

David Newby

Edwin van Beek

Cite this

¹⁸F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial